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RC1 38  .P22  Diphtheria  and  allie 


RECAP 


PABKER 


DIPHTHERIA 


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College  of  3^iiv&itim&  anb  ^urgeong 


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'•viombia  Univere 


DIPHTHERIA 


AND 


•Allied  Pseudo-Membranous  Inflammations 


A    CLINICAL  AND  BACTERIOLOG- 
LCAL   STUDY 


WILLIAM    HALLOCK    PARK,    M.D. 


NEW    YORK 


Repritiied  f7-07n  the  Medical   Record,   July  30  and  August  6, 
1892 


NEW   YORK 

TROW  DIRECTORY,   PRINTIirG  AND  BOOKBINDING  CO. 

201-213  East  Tw  clfth  Street 

1 892 


Diphtheria  and  Allied  Pseudo-Mem- 
branous Inflammations. 

A    CLINICAL   AND   BACTERIOLOGICAL    STUDY* 


The  diagnosis  of  diphtheria  has  always  been  a  subject  of 
extreme' importance  in  medicine. 

Are  all  cases  of  diffuse  pseudo  membranous  inflamma- 
tion of  the  upper  air-passages,  and  all  cases  of  membra- 
nous laryngitis,  rhinitis,  and  tonsillitis  the  local  manifesta- 
tion of  one  disease — diphtheria  ?  Are  all  these  cases 
equally  contagious  and  equally  dangerous?  These  are 
questions  which  occur  daily  to  the  minds  of  practi- 
tioners. 

The  marked  differences  noticed  in  different  cases  have 
always  forced  on  physicians  the  possibility  that,  under  the 
term  diphtheria,  we  may  include  more  than  one  disease. 
When  it  was  discovered  that  two  different  conditions  ex- 
isted in  pseudo- membranous  inflammations  it  was  hoped 
that  here  we  had  a  reliable  diagnostic  sign.  One  is  a 
gangrenous  inflammation,  in  which  there  is  superficial  ne- 
crosis, leaving  on  the  removal  of  the  adherent  pseudo - 
membrane  a  bleeding  surface  ;  the  other  is  an  exudative 
inflammation,  leaving  on  the  removal  of  the  loosely  at- 
tached deposit  an  intact  surface.  The  first  was  sup- 
posed to  occur  in  true  diphtheria,  the  second  as  a  result 
of  some  local  irritant,  either  chemical  or  bacteriological. 
Experience  proved  this  test,  like  so  many  others,  unreli- 
able, and  most  clinical  observers  still  thought  it  wisest  to 
consider  all  pseudo  membranous  inflammations  as  if  they 
were  the  local  expression  of  the  acute  infectious  disease 
which  we  call  diphtheria. 

Since  the  discovery  of  the  existence  of  bacteria,  and  of 
their  relation  to  disease,  a  new  hope  has  arisen  that  by 
the  bacteriological  examination  of  these  pseudo-mem- 
branes we  might  get  a  truer  knowledge   of  the  disease 

*  Alumni  Association  College  of  Physicians  and  Surgeons  Prize  Es- 
say, with  additional  cases. 


4  DIPHTHERIA    AND    ALLIED 

called  diphtheria,  and  settle  the  question,  whether  or  no, 
under  this  name  we  should  include  more  than  one  dis- 
ease. At  the  outset  the  difficulties  were  very  great,  owing 
to  the  multitude  of  bacterial  forms  present  in  the  mouth. 
However,  persistent  investigation,  aided  by  the  improved 
methods  of  bacteriological  study,  has  overcome  all  these 
obstacles. 

Although  recent  reviews  by  Loeffler,'  Welch, ^  and 
others  makes  it  almost  unnecessary,  it  is  thought  best,  in 
order  to  have  the  whole  subject  fresh  in  mind,  to  give  as 
briefly  as  possible  the  reasons  which  have  led  to  the  ac- 
ceptance of  the  Klebs-Loeffler  bacillus  as  the  cause  of 
true  diphtheria,  this  sketch  to  be  followed  by  a  summary 
of  the  chief  characteristics  of  the  bacillus,  and  the  more 
important  lesions  produced  by  it.  Finally,  to  present  the 
evidence  that  a  streptococcus  is  the  most  frequent  agent 
of  infection  in  cases  of  pseudo-membranous  inflammation 
in  which  the  Klebs-Loeffler  bacillus  is  absent. 

True  Diphtheria. — In  the  year  1883,  Klebs  ^  demon- 
strated, morphologically,  the  constant  occurrence  of  a 
bacillus  in  the  pseudo  membranes  of  those  subject  to  epi- 
demic diphtheria.  Loeffler,*  in  1884,  published  the  re- 
sults of  a  very  thorough  and  extensive  series  of  investiga- 
tions. He  found  the  bacillus  described  by  Klebs  in  the 
pseudo-membranes  in  nearly  all  cases  examined.  He 
proved  by  inoculating  that  this  bacillus  was  pathogenic 
in  certain  animals.  When  inoculated  on  the  injured  mu- 
cous membrane  it  produced  a  pseudo-membrane  some- 
what like  that  present  in  human  diphtheria.  He  failed 
to  find  the  Klebs  bacillus  either  in  the  blood  or  organs 
of  fatal  cases  of  human  diphtheria,  or  in  the  same  re- 
gions of  animals  dying  after  inoculation.  He  came  to 
the  conclusion  that  the  Klebs  bacillus  was  the  probable 
cause  of  true  diphtheria.  He  considered,  however,  that 
further  investigations  were  necessary  to  prove  his  conclu- 
sion. 

Since  then  the  whole  subject  has  been  examined  with 
great  care,  not  only  by  Loefiler  himself,  but  also,  inde- 
pendently, by  a  large  number  of  investigators,  both  in 
Europe  and  America.  The  work  of  Roux  and  Yersin,^ 
in  Paris;  Loeffler,  in  Berlin  ;  Kolisko  and  Paltauf,"  in  Vi- 
enna; Ortmann,' in  Konigsberg;  Zarniko,^  in  Kiel;  Es- 
cherich,"  in  Munich;  Beck,'"  Brieger,"  and  Fraenkel,'^in 
Berlin  ;  Tangl,''  in  Tubingen;  Babes,''  in  Bucharest;  d'Es- 
pine,"  in  Geneva;  Klein, '"  in  London  ;  Welch  and  Ab- 
bott,''^  in  Baltimore  ;  Prudden,''  in  New  York,  and  many 
others,  has  established  that  in  all  cases  of  typical  infec 
tious  diphtheria  the  Klebs-Loeffler  bacilli  are  present  in 
large  numbers  in  the  pseudo -membranes,  either  alone  or 
associated  with  other  bacteria,  and  that  the  Klebs-Loef- 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.  5 

fler  bacilli  in  all  other  inflammations  of  the  throat  and  in 
healthy  throats  are  very  rarely  found„ 

Pseudo-membranes,  paralysis,  and  organic  lesions  can 
be  produced  in  inoculated  animals,  similar  to  those  found 
in  human  diphtheria.  A  toxine  is  produced  by  the  bacilli 
which,  when  isolated  and  inoculated,  produces  the  same 
results,  with  the  exception  of  the  pseudo-membrane,  as 
the  pure  cultures. 

All  the  conditions  have  now  been  fulfilled  which  are 
necessary  to  the  proof  of  the  dependence  of  true  diphthe- 
ria upon  the  bacilli  described  by  Klebs  and  Loe filer. 

The  Klebs-Loefiler  Bacilli. — They  are  moderate-sized 
rods,  usually  slightly  bent,  averaging  nearly  as  long  as  the 
tubercle  bacilli,  but  twice  as  broad  and  usually  with 
rounded  ends.  According  to  the  rapidity  of  growth,  the 
soil,  and  other  conditions,  the  form  and  size  of  the  micro- 
organisms varies,  and  the  differences  are  striking  in  ap- 
pearance. The  bacteria  are  sometimes  enveloped  in  a 
more  or  less  capacious  membrane ;  sometimes  the  con- 
tents divide  into  a  number  of  pieces,  separated  by  trans- 
verse divisions  ;  one  end  of  the  rods  is  frequently  thick- 
ened like  a  club,  or  both  ends  may  be  clubbed,  or  one  or 
both  pointed.  The  bacilli  are  immobile  and  have  no 
spores.  The  best  staining  agent  is  Loeffler's  alkaline 
methyl  blue.  Some  forms  stain  uniformly,  others  in  vari- 
ous irregular  ways,  the  most  common  being  the  appear- 
ance of  deeply  stained  granules  in  a  slightly  stained  bacil- 
lus, or  of  darkly  stained  ends  with  a  paler  centre.  The 
bacilli  are  very  often  in  pairs,  never  in  chains ;  they  are 
semi-anaerobic,  and  thrive  only  at  a  somewhat  high  tem- 
perature, 20°  to  42°  C. 

The  Loeffler  bacilli  can  be  cultivated  upon  all  the 
ordinary  culture-media,  but  grow  most  vigorously  on  a 


Surface  Colony  of  Klebs- Loeffler  Ba-  Klebs-Loeffler  Bacilli,  highly 

cilli,  on  Agar  Plate,  slightly  magni-  magnified, 

fied  ;  twenty  hours'  growth. 

mixture  of  blood  serum  and  nutrient  bouillon,  as  given 
by  Loeffler.  On  this,  solidified,  the  bacilli  grow  as 
large,  round,  elevated,  grayish-white  colonies,  with  the 
centre  more  opaque  than  the  somewhat  irregular  per- 
iphery. 


6  DIPHTHERIA   AND   ALLIED 

Th.e  Sections  of  Diphtheritic  Membrane  show  on  the 
surface  and  in  the  most  superficial  portions  of  the  pseudo- 
membrane  Loeftier  bacilh  mixed  with  more  or  less  nu- 
merous other  micro-organisms.  In  the  middle  and  deep- 
er portions  the  Loeffler  bacilli,  alone  or  associated  with 
streptococci,  are  usually  the  only  organisms  present.  In 
the  deepest  layer  there  are  very  few  bacilli  and  in  the 
mucous  membrane,  as  a  rule,  none.  Extremely  rarely 
they  are  found  in  the  blood  and  viscera.  Some  of  those 
bacteria  which  are  associated  with  the  Klebs-Loeffler  ba- 
cilli in  diphtheria,  especially  the  streptococci,  may  be 
found  in  the  mucous  membrane,  lymphatic  glands,  and 
internal  organs. 

Toxic  Albumins. — The  toxic  albumins  produced  by 
the  diphtheria  bacilli  have  been  especially  investigated 
by  Roux  and  Yersin,-^  and  Fraenkel  and  Brieger.""  This 
toxic  substance  is  of  a  proteid  nature,  precipitated  by 
alcohol,  soluble  in  water.  Nearly  pure,  it  is  a  white, 
amorphous  mass  of  light  specific  gravity,  and  keeps  its 
properties  for  a  long  time  unchanged.  Its  extraordinary 
poisonous  nature  is  shown  by  Roux  and  Yersin,  in  that 
four  tenths  of  a  milligramme  of  the  substance,  when  in- 
oculated, was  sufficient  to  kill  eight  guinea-pigs.  If  this 
poison  be  inoculated  into  a  guinea-pig,  it  produces  all 
the  changes,  except  the  pseudo-membrane,  that  the  pure 
culture  of  the  bacilli  does.  The  long  continuance 
of  the  toxic  power  of  the  poison  in  the  body  and  its 
slow  absorption  from  the  locally  infected  tissues  ac- 
count for  the  deaths  which  occur  some  time  after  the 
entire  disappearance  of  the  bacilli  from  the  infected 
throats. 

The  toxalbumin  of  diphtheria  is  very  little,  if  at  all, 
absorbed  by  intact  mucous  membranes,  and  can  be  swal- 
lowed by  susceptible  animals  in  large  amounts,  without 
danger. 

Lesions. — In  animals  inoculated  with  the  bacilli  or 
these  toxalbumins  we  find  at  the  seat  of  inoculation  a 
grayish  focus  surrounded  by  an  area  of  congestion.  The 
subcutaneous  tissues  for  an  extensive  area  around  are 
congested  and  more  or  less  oedematous.  The  adjacent 
lymph-glands  are  swollen  and  the  serous  cavities  usually 
contain  an  excess  of  clear  or  turbid  fluid.  The  micro- 
scopical changes  in  the  internal  organs  of  animals  dying 
of  experimental  diphtheria  have  been  studied  by  Babes," 
Welch"^  and  Flexnor,  and  others. 

In  the  liver  there  are  found  numerous  smaller  and 
larger  masses  of  necrotic  cells.  These  areas  are  perme- 
ated by  leucocytes.  Congestion  with  hemorrhages  into 
the  capsule  and  tissue  are  present.  In  the  kidneys  fatty 
changes  occur  in  the  epithelium  of  the  tubes  and  glome- 


PSEUDO-MEMBRANOUS    INFLAMMATIONS.  / 

ruli  and  a  hyaline  alteration  of  the  glomerular  capillaries 
and  of  the  smaller  arteries.  In  the  spleen  and  lymph- 
glands  the  necrosis  of  cells  is  also  present.  Both  the 
cell-bodies  and  nuclei  of  living  cells  are  altered.  The 
lungs  show  areas  of  intense  congestion  with  hemorrhages 
into  their  tissue.  The  heart  is  nearly  always  the  seat  of 
fatty  degeneration.  The  fibres  of  the  voluntary  muscles 
show  degenerative  changes.  The  number  of  leucocytes 
is  greatly  increased  in  the  blood. 

Experimental  Immunity. — The  exceedingly  interest- 
ing results  obtained  by  Fraenkel,  Behring,^'  Brieger,^*  and 
others  '^  in  producing  immunity  in  animals,  gives  the  hope 
at  least  of  practical  results  in  the  future.  They  found 
that  the  blood  or  serum  of  animals  rendered  immune 
against  diphtheria  had  the  power  of  rendering  other  ani- 
mals, when  injected  into  their  bodies,  also  immune.  In 
animals  already  infected  the  injections  had  the  power  of 
destroying  or  neutralizing  the  poison  secreted  by  the  ba- 
cilli. It  was  also  found  that  the  offspring  of  immune 
animals  possessed  a  considerable  degree  of  immunity. 
Their  success  in  treating  animals  has  been  so  great  that 
the  endeavor  to  cure  human  diphtheria  is  soon  to  be 
made.  , 

Duration  of  Life  in  the  Kiebs-Loeffler  Bacilli. — The 
life  of  the  bacillus  varies  greatly  according  to  the  condi- 
tions under  which  it  is  placed.  An  agar  tube-culture  in 
the  laboratory  is  still  alive  after  seven  months'  growth,  and 
a  bit  of  membrane  no  larger  than  a  pin's  head  still  gives 
cultures  of  both  the  bacilli  and  the  streptococci  four 
months  after  its  removal  from  the  throat.  Some  have 
found  bits  of  membrane  kept  in  cloth  to  be  still  alive 
after  six  months.  Probably  in  dark,  damp,  dirty  places 
life  remains  even  longer,  while,  on  the  other  hand,  under 
unfavorable  conditions  the  bacilli  may  live  only  a  few 
days. 

The  Conditions  Necessary  for  the  Infection  of  Man 
with  the  contagium  of  diphtheria  are  of  great  practical  im- 
portance. Whether  this  can  be  implanted  on  the  normal 
mucous  membrane  in  man  is  still  a  question.  Undoubt- 
edly a  lesion  favors  it.  When  the  Klebs-Loeffler  bacilli 
are  implanted  on  the  normal  mucous  membranes  of  sus- 
ceptible animals  they  do  not  grow.  The  researches  of 
Barbier  "°  throw  interesting  light  on  this  subject  He  found 
that  a  streptococcus  which  was  associated  with  the  Loef- 
fier  bacillus  in  all  cases  where  marked  redness  and  swell- 
ing were  present,  when  implanted  on  the  normal  mucous 
membrane  of  the  vagina  in  guinea-pigs,  produced  an 
acute  purulent  discharge,  with  redness  and  swelling.  If 
with  these  cocci,  or  even  four  weeks  later,  the  Loeffler 
bacilli  were  brought  into  contact  with  the  mucous  mem- 


8  DIPHTHERIA   AND   ALLIED 

brane,  a  severe  diphtheritic  irflammation  was  started 
which  often  caused  death.  If  these  results  can  be  ap- 
pHed  to  man,  they  add  a  new  importance  to  the  discov- 
ery that  streptococci  are  frequently  present  in  slightly  in- 
flamed throats,  and  to  their  frequent  association  in  the 
pseudo-membranes  with  the  Loeffler  bacilli. 

Psendo- Diphtheria  Bacillus. — The  relation  of  this  ba- 
cillus to  that  of  true  diphtheria  is  of  much  practical  im- 
portance. Abbott  "  has  recently  given  such  an  exhaustive 
review  of  this  subject  that  it  will  only  be  necessaiy  here 
to  give  a  brief  summary.  The  term  is  now  used  to  de- 
fine a  group  of  bacilli  which  closely  resemble  the  Loef- 
fier,  but  which  are  without  pathogenic  properties  in  guinea- 
pigs.  By  some  writers  the  term  is  used  to  cover  varieties 
that  show  quite  marked  cultural  and  morphological  dif- 
ferences. 

It  has  been  established  that  bacilli  with  all  the  charac- 
teristics of  the  Klebs-Loeffler,  except  their  virulence,  are 
to  be  found  exceptionally  where  pseudo-membranes  are 
absent.  These  are  never  numerous,  only  a  few  scattered 
colonies  being  found  on  plates  or  tubes.  In  some  locali- 
ties they  are  found  rather  frequently,  in  others  rarely,  or- 
not  at  all.  Roux  and  Yersin  ^^  found  also  that  among 
those  obtained  from  cases  of  diphtheria  there  were  gra- 
dations in  virulence  from  those  whose  inoculation  caused 
death  in  guinea  pigs  in  twenty-four  hours  to  those  which 
produced  only  local  changes.  They  found  that  those 
taken  from  mild  cases  are,  as  a  rule,  the  least  virulent. 
Beck  found  in  some  cases  of  true  diphtheria  both  viru- 
lent and  non-virulent  bacilli. 

As  the  result  of  a  large  number  of  experiments,  Roux 
and  Yersin  hold  that  the  morphological  and  cultural  dif- 
ferences between  the  diphtheria  and  the  pseudo-diph- 
theria bacilli  are  inconstant,  and,  when  present,  are  in- 
sufificient  to  establish  that  they  belong  to  different  species. 
In  this  country  the  pseudo-diphtheria  bacilli  have  been 
infrequently  found.  Prudden,  in  a  large  number  of 
cases  in  New  York,  did  not  find  them  once.  Koplik  has 
found  them  a  few  times,  and  Abbott  in  fifty-three  cases  in 
four.  In  these  studies  the  pseudo-diphtheria  bacilli  were 
met  with  only  once,  as  proved  by  animal  experiments. 
This  whole  subject  needs  further  study. 

For  bedside  diagnosis  all  cases  which  give  typical  colo- 
nies of  bacilli  resemWing  the  Klebs  Loeffler  should  be 
regarded  as  true  diphtheria ;  both  because  of  the  length 
of  time  consumed  in  animal  experiments  and  of  the  im- 
possibility of  being  sure  that  because  the  colony  from 
which  the  inoculating  culture  was  made  was  not  virulent 
all  the  colonies  were  the  same.  This  merely  compels  a  few 
doubtful  cases  of  diphtheria  to  be  still  considered  as  such. 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.  9 

Pseudo-membranous  Inflammations  in  which  the  Klebs- 
Loeffler  Bacillus  is  Absent. — The  presence  of  strepto- 
cocci in  the  pseudo  membranes  and  in  the  blood  of  fatal 
cases  of  diphtheria  has  been  known  for  many  years. 
Loeffler,^'  in  1884,  described  a  class  of  cases  where  loss 
of  substance  with  a  gray  yellow  or  necrotic  base  was  a 
characteristic  feature  in  which  the  Klebs-Loeffler  bacil- 
lus was  absent,  but  a  streptococcus  very  abundant.  He 
concluded  that  in  these  cases  the  frequency  of  the  pres- 
ence of  the  streptococci  either  means  that  the  poison  of 
diphtheria  has  been  at  first  present,  and  thus  prepared 
the  way  for  the  streptococci,  and  then  vanished  before 
examination,  or  that  the  streptococci  are  the  cause  of 
this  peciiliar  form  of  pseudo-membranous  inflammation. 
He  came  to  the  conclusion  that  the  first  supposition  was 
the  true  one,  that  the  streptococci  were  secondary  to  the 
Klebs-Loeffler  bacilli. 


■■^'^irf*H. 


h^^i^ 


Streptococcus  Colony,  slightly  magnified  ;  Streptococci,  highly  mag- 

twenty  hours'  growth.  nified. 

This  streptococcus  he  isolated  in  three  cases  from  the 
tonsils  and  in  two  cases  from  the  internal  organs.  Both 
the  biological  characters  and  the  general  effects  upon 
inoculated  animals  seemed  to  indicate  a  close  relation- 
ship with  the  streptococcus  pyogenes  and  erysipelatus. 
The  changes  produced  upon  the  mucous  membrane  by 
its  inoculation  did  not  resemble  closely  the  cnaracteristic 
local  lesions  of  diphtheria.  From  that  time  until  the 
present  year  it  seemed  to  be  the  aim  in  Europe,  espe- 
cially in  Germany,  to  seek  out  for  examination  only  typ- 
ical cases  of  epidemic  infectious  diphtheria.  In  these 
cases  the  Klebs  Loefifler  bacilli  were  constantly  found, 
and  they  came  to  be  looked  upon  more  and  more  as  the 
only  etiological  cause  of  all  extensive  pseudo-membra- 
nous inflammations,  at  least  when  they  were  not  compli- 
cations of  infectious  diseases. 

In  1889,  Prudden  ^°  published  the  results  of  a  very 
careful  bacteriological  investigation  of  twenty-four  cases 
of  fatal  pseudo  membranous  inflammation  of  the  tonsils, 
pharynx,  and  larynx,  which  were  all  considered  clinically 


lO  DIPHTHERIA   AND    ALLIED 

to  be  diphtheria.  These  cases  were  mostly  young  chil- 
dren in  two  asylums  where  they  had  been  exposed  to 
scarlet  fever  and  measles,  and  in  some  of  whom  these 
diseases  had  existed  as  a  complication.  In  not  one  of 
these  were  the  Klebs-Loeffler  bacilli  found,  but  in  all 
but  two  streptococci.  These  were  present  in  most  of 
the  cases  in  enormous  numbers,  as  shown  by  the  cultures. 
In  three  cases  in  which  the  viscera  were  examined  they 
were  found  to  contain  a  moderate  number  of  strepto- 
cocci. In  the  ducts  of  the  mucous  glands  and  in  the 
lymph-spaces  of  the  submucosa,  the  streptococci  were 
found  in  greater  or  smaller  numbers,  also  rarely  in  the 
tracheal  and  bronchial  glands.  The  staphylococcus  py- 
ogenes aureus  and  albus  were  present  in  varying  num- 
bers, but  hardly  more  frequently  than  in  many  apparently 
normal  throats. 

In  sixteen  of  the  twenty  four  cases,  broncho-pneu- 
monia ^'  was  present,  and  cultures  made  from  the  fresh 
broncho-pneumonic  areas  in  fifteen  of  these  gave  large 
numbers  of  streptococci.  The  streptococci  obtained 
from  all  these  cases  presented  the  same  morphological 
and  biological  characters.  They  appeared  to  be  identi- 
cal with  the  streptococcus  pyogenes. 

From  his  investigations  Prudden  concluded  that  in  a 
certain  class  of  cases  pseudo-membranes  were  caused  by 
streptococci.  Kolisko  and  Paltauf,  Wurz  and  Bourges,^" 
Sevestre,^^  Tangl,^*  Baginsky,^^  and  others  have  found 
streptococci  but  no  Loeffler  bacilli  in  the  pseudo-mem- 
branous inflammations  occurring  early  in  scarlet  fever. 
Baginsky,^^  in  his  recent  studies,  found  that  in  one  hun- 
dred and  fifty-four  cases  clmicaily  diagnosed  as  diph- 
theria, there  were  thirty- four  in  the  pseudo-membranes  of 
which  no  Loeffler  bacilli  were  present.  In  two  cases  of 
membranous  rhinitis  he  found  the  bacilli  present.  These 
ran  the  usual  mild  course. 

Martin,^'^  in  Paris,  has  just  pubUshed  a  clinical  and 
bacteriological  study  of  the  croupous  deposits  of  two 
hundred  children  suspected  of  diphtheria.  He  found  in 
seventy-two  no  Klebs  Loeffler  bacilli;  of  these,  twenty- 
nine  were  croup  cases.  The  mortality  of  these  was  far 
less  than  in  those  having  true  diphtheria.  Some  of  the 
children  had  been  exposed  to  scarlet  fever  and  measles. 
He  is  of  the  opinion  that  the  certain  clinical  diagnosis  of 
these  cases  is  impossible.  A  few  examples  of  infection 
with  diphtheria  in  the  wards  are  given.  He  regards  the 
association  of  different  bacteria  with  the  Loeffler  bacilli 
as  greatly  modifying  the  course  of  the  disease.  As  he 
used  only  blood-serum  tubes,  he  probably  has  often 
overlooked  the  almost  invisible  colonies  of  the  strep- 
tococci.    He  also  believes  that  from  the  form  of   the 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.        II 

Klebs-Loefifler  bacilli  one  can  judge  somewhat  of  their 
virulence. 

Aim  and  Scope  of  these  Investigations. — The  object 
of  these  studies  has  been  to  determine  by  the  bacterio 
logical  examination  of  a  large  number  of  cases  whether, 
in  fact,  pseudo  membranous  inflammations  can  be  divided 
into  two  distinct  classes,  and,  if  so,  in  what  proportion  of 
the  cases  the  Klebs-Loeffler  bacilH  are  present ;  also  to 
go  further  and  see  if,  by  combining  in  all  cases  a  very 
careful  clinical  examination  with  a  bacteriological  one,  it 
would  not  be  possible  to  iind  some  constant  differences 
between  the  local  appearances  and  general  symptoms  of 
true  diphtheria  and  those  pertaining  to  other  croupous 
inflammations. 

The  cases  recorded  in  the  following  pages  include  all 
those  having  pseudo-membranous  inflammations  admitted 
to  the  wards  of  the  Willard  Parker  Hospital  during  four 
consecutive  months  ;  also  a  number  sent  to  me  by  sev- 
eral physicians,  and  six  cases  of  membranous  rhinitis 
from  the  throat  classes  of  the  Vanderbilt  Clinic  and  the 
Roosevelt  Hospital. 

In  all,  one  hundred  and  fifty-nine  were  examined ; 
these  will  be  studied  in  the  following  classes  :  True 
diphtheria,  those  in  which  the  Klebs-Loeffler  bacilli  are 
present  alone  or  with  other  bacteria ;  pseudo-diphtheria, 
those  in  which  the  Klebs-Loeffler  bacilli  were  never  pres- 
ent, but  some  form  of  cocci,  usually  streptococci. 

For  comparison,  the  following  were  also  examined 
bacteriologically  :  FoUicular  tonsillitis,  lo  ;  peritonsillar 
abscess,  5  ;  acute  pharyngitis,  5  ;  chronic  pharyngitis,  5  ; 
hyper aemic  throats  m  scarlet  fever,  10. 

Technical  Observations. — To  obtain  the  material  for 
examination  two  methods  were  employed.  Where  a 
piece  of  membrane  could  be  removed  without  injuring 
the  throat,  this  was  done  by  means  of  along,  slender  pair 
of  forceps,  carefully  sterilized.  For  the  cases  in  which 
this  was  impossible,  a  number  of  cotton  plugs  *  had  been 
prepared  by  wrapping  small  portions  of  absorbent  cotton 
around  the  ends  of  slender  sticks,  one  inch  in  length, 
which  were  then  placed  in  a  tube  and  sterilized  by  dry 
heat.  Taking  one  of  these  in  the  forceps,  it  was  rubbed 
gently,  but  rather  firmly,  against  any  visible  pseudo-mem- 

*  In  a  number  of  trials,  in  which,  from  the  same  cases,  plates  were 
made  both  from  bits  of  membrane  and  from  the  swabs,  the  latter 
proved  as  trustworthy  as  the  former.  For  the  use  of  physicians,  who 
supplied  me  with  cases  from  outside  the  hospital,  I  kept  a  number  of 
strong  glass  tubes,  two  and  one-half  inches  in  length  by  one-half 
inch  in  thickness.  Each  tube  contained  an  absorbent  cotton  swab, 
and  was  plugged  with  cotton.  The  tubes  and  their  contents  were  then 
placed  in  the  hot-air  sterilizer.  These  could  be  carried  in  the  pocket. 
After  use  at  the  bedside  they  were  returned  to  the  laboratory,  where 
the  plates  and  tubes  were  made. 


12  DIPHTHERIA   AND   ALLIED 

brane  ;  when  none  was  present,  the  cotton  was  rubbed 
against  the  tonsils  and  pharynx.  The  bit  of  membrane 
or  cotton  plug  was  then  gently  drawn  three  or  four  times 
across  the  surface  of  a  six  per  cent,  glycerine-agar  Petri 
plate,  making  equally  distant  lines  of  inoculation.  Taken 
to  the  laboratory,  here  the  bit  of  membrane  or  swab  was 
drawn  across  a  blood-serum  tube  and  then  rubbed  in  a 
few  drops  of  sterilized  water.  With  a  sterilized  platinum 
loop  a  drop  of  this  turbid  fluid  was  taken  up  and  drawn 
across  t^o  or  more  solidified  Loeffler's  blood-serum  tubes, 
and  a  second  drop  across  a  second  agar  plate.  The  tubes 
and  plates  were  placed  in  the  thermostat  and  kept  at 
37°  C.  for  twenty -four  hours.  From  the  membrane,  or 
swab,  two  cover-glass  smears  were  prepared,  stained  with 
Loeffler's  methyl  blue  solution,  studied  under  the  micro- 
scope, and  the  forms  of  bacteria  seen  recorded.  On  the 
following  day  the  colonies  of  the  Loeffler  bacilli,  when 
present,  in  every  case  had  reached  a  size  sufhcient  to  be 
distinctly  seen  on  both  the  blood-serum  tubes  and  agar 
plates,  and,  under  the  microscope,  showed  their  extremely 
characteristic  appearance  on  the  latter. 

It  is  necessary  to  be  extremely  careful  to  have  the 
glycerine  agar  famtly  alkaline,  to  have  proper  peptone,  and 
to  use  only  fresh,  moist  plates,  otherwise  there  may  result 
an  entire  failure  to  get  any  growth  of  the  Loeffler  bacilli. 

In  these  investigations  the  special  object  in  view  was 
to  discover  in  the  cultures  the  presence,  or  absence,  as 
well  as  the  relative  abundance  of  the  Klebs-Loeffler  ba- 
cilli, the  streptococci,  and  the  staphylococci.  Any  other 
forms  of  bacteria  that  appeared  frequently  or  in  large 
numbers  were  also  investigated. 

The  Comparative  Value  as  Culture-media  of  Blood-se- 
rum and  Six-per-cent.  Glycerine-Agar.— On  the  solidified 
blood-serum  mixture  suggested  by  Loeffler  the  Klebs- 
Loeffler  bacilli  grow  more  rapidly  and  surely  than  on  any 
other  of  the  usual  solid  media.  The  growth  of  the  colo- 
nies, though  fairly  uniform,  is  not  sufficiently  characteristic 
to  certainly  identify  them,  for  certain  frequently  present 
cocci  grow  with  almost  the  same  rapidity  and  appearance. 
The  usefulness  of  the  serum  is  limited  to  tubes,  from  its 
slight  cloudiness  and  the  great  difficulty  of  making  plates. 

On  glycerine-agar  the  growth  of  the  bacilli  is  less 
rapid,  but  still  vigorous  when  made  from  fresh  bits  of  mem- 
brane or  swabs.  The  gross  appearance  of  the  colonies 
is  here  also  very  similar  to  those  of  several  forms  of 
cocci.  The  appearance  of  the  colonies  under  the  micio- 
scope  is,  on  the  other  hand,  extremely  characteristic  and 
entirely  different  from  those  of  any  other  bacteria  occur- 
ring in  the  throat,  with  the  possible  exception  of  the 
pseudo-diphtheria   bacilli.      Glycerine-agar    in   tubes  is 


MEDICAL  RECORD. 


July   5oth,  1802. 


PHOTOGRAPHS    OF    PLATE    CULTURES    FROM    DIPHTHERIA   AND    SCARLATINA- Park 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.        I  3 

much  less  useful  than  the  serum,  but  in  plates  it  has  many 
great  advantages,  and  if  it  were  not  that  under  certain  con- 
ditions, when  still  capable  of  growing  on  the  blood  serum, 
the  Loeffler  bacilli  are  unable  to  grow  on  the  agar,  the  agar 
plates  could  entirely  replace  the  serum  tubes.  This  ab- 
sence of  growth  on  agar  has  occurred  in  two  cases  where 
frequent  irrigation  with  i  to  4., 000  bichloride  of  mercury 
had  been  employed,  also  from  two  long-dried  swabs. 

In  disinfection  work,  cultures  would  be  obtained  on 
blood  serum  when  they  no  longer  appeared  on  the  agar. 
With  these  exceptions  the  plates  always  contained  colonies 
of  the  Loeffler  bacilli  whenever  the  tubes  contained  them. 

Throat  cultures  show  the  most  characteristic  growth 
under  the  microscope  when  the  plates  are  examined  after 
remaining  from  sixteen  to  twenty-four  hours  in  the  ther- 
mostat. The  colonies  of  the  different  bacteria  common 
to  the  throat  have  then  attained  a  characteristic  growth 
and  are  still  for  the  most  part  distinctly  separate.  At 
this  time,  after  some  familiarity  with  the  work,  you  can 
rapidly  run  over  the  plates,  placed  under  the  microscope, 
with  a  low  power  lens,  and  acquire  a  knowledge  not  only 
of  how  many  varieties  of  organisms  are  present  but  also 
the  relative  proportion.  The  colonies  can  then  be  further 
studied  by  a  higher  power  lens  and  under  the  microscope 
accurately  fished. 

For  the  photographs  of  six  of  the  plate  cultures,  shown 
in  the  accompanying  Plate,  I  have  to  thank  my  friend  Dr. 
Edward  Learning.  These  give  the  usual  appearance  of 
the  plates  made  from  fresh  membranes  or  swabs.  At 
times  the  colonies  are  much  closer  together,  at  other 
times  less  so  than  in  these.  They  show  at  a  glance  the 
actual  and  relative  size  of  the  colonies,  and  to  some 
extent  their  appearance  after  twenty  to  thirty  hours' 
growth  at  37°  C.  It  can  be  readily  seen  how  thor- 
oughly the  isolated  colonies  can  be  investigated  when  the 
uncovered  plate  is  put  on  the  microscope- stand  and  each 
colony  individually  studied  with  any  power  lens  desired. 

Explanation  of  Plate. 

Figs.  I  and  2  show  cultures  from  same  diphtheritic  membrane — i, 
with  numerous  ;  2,  with  fewer  colonies.  The  more  numerous  colonies 
are  composed  of  diphtheria  bacilli;  the  larger  whiter  ones  of  non- 
pathogenic bacilli. 

Fig.  3,  pure  culture  of  diphtheria  bacilli  from  tissue  of  inoculated 
guinea-pig. 

Fig.  4,  culture  obtained  by  pressing  a  portion  of  a  soiled  sheet,  re- 
moved from  a  diphtheria  patient,  against  the  media  surface.  Many- 
varieties  of  bacteria  grew.  The  smaller  colonies  are  diphtheria  ba- 
cilli and  streptococci. 

Fig.  5,  a  pure  culture  of  streptococci  from  scarlatinal  membrane. 

Fig.  6,  culture  from  croupous  tonsillitis.  The  exceedingly  small 
colonies  are  streptococci.  Some  of  moderate  size,  staphylococci. 
No  diphtheria.  In  both  5  and  6  the  condensation  water  has  swept  the 
bacteria  over  the  plate  surface,  making  a  diffuse  growth  of  colonies. 


14  DIPHTHERIA   AND   ALLIED 

Glycerine-agar  plates  in  which  the  media  has  been 
tested  are  sufficient  when  the  cultures  are  to  be  made 
immediately  from  throats  in  which  frequent  antiseptic 
irrigation  has  not  been  used.  Whenever  the  bacilli  may 
have  been  injured  from  antiseptics,  drying,  or  any  other 
cause,  the  blood-serum  tubes  should  also  be  used  to  in- 
sure the  growth  of  the  Loeffler  bacilli. 

For  the  simple  determination  of  the  presence  or  ab- 
sence of  the  Loeffler  bacilli  the  blood-serum  suffices. 
I  believe  that  the  failure  to  fully  recognize  that  there  are 
many  extensive  pseudo-membranes,  neither  due  to  the 
Loeffler  bacillus  nor  occurring  after  scarlatina,  is  owing 
to  the  almost  exclusive  use  of  blood  serum  tubes,  since  in 
tubes  it  is  impossible  to  satisfactorily  use  the  microscope 
to  identify  the  smaller  colonies,  and  before  they  become 
visible  to  the  eye  they  are  often  overgrown  by  the  more 
rapidly  growing  bacteria. 

When  the  colonies  of  the  bacteria  sought  for  were 
plainly  isolated,  tube  cultures  were  immediately  made 
from  a  characteristic  colony  ;  when  not,  a  sowing  was 
made  on  a  fresh  plate  and  isolated  colonies  obtained. 

Animal  Inoculations. — From  the  first  or  second  genera- 
tion of  the  Klebs  Loeffler  bacilli,  tubes  of  faintly  alka- 
line nutrient  bouillon  were  inoculated.  The  tubes  were 
removed  from  the  thermostat  on  the  fourth  day.  Two- 
thirds  of  the  clear  bouillon  was  poured  off  and  the  re- 
mainder well  shaken.  One-third  cubic  centimetre  of  this 
fluid,  turbid  with  the  bacilli,  was  inoculated  into  the  sub- 
cutaneous tissue  of  the  side  of  the  abdomen  of  a  guinea- 
pig.  Guinea-pigs  were  inoculated  from  cultures  of  twenty- 
two  of  the  cases  in  which  the  Klebs-Loeffler  bacilli 
were  present.  In  nineteen  death  followed  with  typical 
pathological  changes.  In  no  case  were  the  bacilli,  or  any 
other  bacteria,  obtained  in  the  cultures  made  from  the 
heart's  blood,  the  liver,  or  spleen.  In  no  case  were  any 
other  pathogenic  bacteria  than  the  Kleb5-Loeffler  bacilli 
obtained  from  the  cultures  made  from  the  cedematous 
fluid  and  congested  tissue  in  the  immediate  neighborhood 
of  the  point  of  inoculation. 

The  temperature  in  the  animals  fell  after  inoculation 
in  every  case  but  one,  in  which  a  temporary  rise  occurred, 
and  remained  from  one  to  three  degrees  below  the  nor- 
mal until  death. 

The  streptococci  taken  from  four  cases  of  true  diph- 
theria and  from  four  cases  of  pseudo  membranes  in 
which  the  Loeffler  bacilli  were  absent  were  inoculated  in 
rabbits.  The  temperature  of  the  rabbits  rose  after  inocu- 
lation, in  every  case,  from  one  to  five  degrees.  In  two 
local  abscess  and  sloughing  of  tissue  occurred.  In  three 
temporary  swelling  and  redness  and  in  three  no  reaction 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.        I  5 

appeared.  Four  died  between  the  fourth  and  fifth 
weeks.  No  streptococci  were  obtained  from  either  the 
blood  or  viscera  of  the  fatal  cases. 

Description  of  the  Willard  Parker  Hospital. — This 
hospital  is  under  the  control  of  the  New  York  City  Board 
of  Health  and  to  it  are  sent  diphtheria  and  scarlet-fever 
cases.  The  diphtheria  wards,  in  which  the  majority  of 
the  cases  here  studied  were  treated,  comprise  three  large, 
high  rooms,  connected  by  a  hallway.  Two  are  used  for 
the  women  and  children,  and  one  for  the  men.  As  far 
as  possible,  the  convalescent  and  doubtful  cases  are 
separated  from  those  having  true  diphtheria  ;  but  owing 
to  the  frequently  crowded  condition  of  the  wards,  this 
often  cannot  be  done.  The  floors  are  of  hard  wood,  and 
are  washed  daily  with  i  to  i,ooo  bichloride  solution. 
The  iror-  bedsteads  are  carbolized  each  morning.  Where 
patients  soil  their  beds,  the  sheets  and  spreads  are  changed 
daily ;  in  other  cases,  v/eekly.  All  patients  have  their 
nostrils  and  throats  syringed  with  a  i  to  4,000  bichloride; 
solution,  the  bad  cases  every  half  hour,  the  convalescents 
three  times  a  day.  No  swabbing  of  throats  is  allowed. 
All  clothes  brought  to  the  hospital  are  disinfected,  and 
are  only  returned  when  patients  leave.  Patients  are  also 
required  to  take  a  bath  when  they  go  (also,  if  possible, 
when  they  come),  washing  the  hair  with  a  i  to  1,000  bi- 
chloride of  mercury  solution. 

Cases  of  laryngeal  dyspnoea  when  urgent,  or  when  not 
relieved  by  vomiting  and  calomel  fumigations,  are  intu- 
bated. The  only  routine  constitutional  treatment  is  to 
give  alcoholic  stimulants  throughout  the  course  of  the 
disease  to  those  showing  any  tendency  to  heart  failure. 
Tube  cases  are  fed  lying  on  the  lap  with  lowered  head. 
These  details  are  necessary  to  show  the  conditions  under 
which  the  patients  were  placed,  and  to  avoid  a  repeti- 
tion of  the  account  of  the  treatment  in  the  clinical 
histories  which  follow.  The  wards  for  scarlet  fever 
are  on  a  different  floor,  and  have  the  same  arrangement 
of  rooms. 

Methods  of  Clinical  Study. — I  made  daily  rounds  with 
Dr.  Lester,  the  resident  physician  ;  each  case  was  care- 
fully observed,  the  appearance  of  the  throat,  and  the 
complicating  conditions  of  the  larynx  and  nostrils  were 
noted.  As  far  as  possible  sketches  were  made,  and  the 
changes  occurring  from  day  to  day  noticed.  The  figures 
for  pulse,  temperature,  and  respiration  were  taken  from 
the  hospital  charts — the  temperature  in  children  being 
always  taken  by  the  rectum,  in  adults  by  axilla.  The 
urine  analyses  were  also  obtained  from  the  hospital  rec- 
ords. Cultures  were  made  from  every  case  on  the  day 
of   admission,  those  which   showed  very  numerous  col 


1 6  DIPHTHERIA   AND    ALLIED 

onies  of  the  Loeffler  bacilli  were  not  examined  again  for 
three  days,  and  then  every  other  day  till  the  bacilli  had 
twice  proved  absent.  Cultures  were  made  twice  from 
cases  of  croupous  tonsillitis.  Those  having  croupous 
laryngitis  were  examined  daily,  until  all  doubt  as  to  the 
presence  or  absence  of  the  Loeffler  bacilli  was  dispelled, 
s;vabs  and  bits  of  coughed-up  membrane  being  used. 
The  same  care  was  taken  in  extensive  pseudo-membranous 
inflammations,  in  which  the  Loeffler  bacilli  were  absent. 
During  the  last  six  weeks  some  of  the  cases  were  subjected 
to  only  one  thorough  bacteriological  examination. 

True  Diphtheria  (Clinical  histories  and  bacterial  exam- 
inations of  27  illustrative  cases  from  the  54  in  which  the 
Klebs  Loeffler  bacilli  were  present). — The  aim  is  to  pre- 
sent in  the  histories  only  the  most  important  points. 

Case   I.     February   6th. — Molly    F ,    aged    five ; 

membranous  laryngitis ;  intubation;  death.  Chnical  his- 
tory :  Well  nourished  ;  admitted  with  marked  laryngeal 
dyspnoea;  slight  adherent  patches  on  tonsils;  no  pain  on 
opening  mouth ;  no  swelling  of  glands  of  neck.  Tempera- 
ture, 101°  F.;  pulse,  118;  respiration,  34.  Vomiting  and 
fumigations  not  relieving  the  dyspnoea,  she  was  intubated. 

February  9th. — Temperature  has  remained  between 
100  and  loi"^  F. ;  pulse  and  respiration  remain  about 
the  same.  Patient  is  very  languid,  and  has  at  times  dysp- 
noea, which  is  relieved  by  calomel  fumigations.  Patches 
still  remain  on  tonsils. 

February  12th. — Tonsils  clean.    Condition  unchanged. 

February  i8th. — Temperature  normal.  Tube  re- 
moved, 

March  2d. — Patient  taken  home ;  she  is  weak,  can 
hardly  stand,  and  cannot  speak  above  a  whisper.  Since 
the  tenth  day  considerable  quantities  of  albumin  have 
been  present  in  the  urine.     Considerable  emaciation. 

March  nth. — Patient  returned  for  laryngeal  dyspnoea, 
apparently  due  to  laryngeal  paresis.     She  was  intubated. 

March  24th. — Tube  removed.  Patient  is  anaemic ; 
muscles  are  somewhat  atrophied;  some  albumin  per- 
sists in  urine.     Remains  in  bed. 

March  28th. — Is  sitting  up  and  gaining  slightly  in 
strength.  Returned  home.  Died  two  weeks  later  at 
home,  apparently  from  nephritis. 

Bacterial  examination  :  Cover  glass  smear  showed 
many  fairly  typical  Loeffler  bacilh.  Plates  and  tubes 
showed  almost  a  pure  culture  of  vigorous  growing  col- 
onies of  the  Klebs-Loeffler  bacilli.  A  colony  was  re- 
plated,  and  from  this  new  growth  a  bouillon  tube  was 
inoculated.  A  guinea-pig  inoculated  with  i  c.c.  of 
bouillon  culture  died  in  forty-three  hours  with  character- 
istic lesions.     A  pure  culture  of  the  Loeffler  bacilli  was 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.        1/ 

obtained  from  the  tissue  at  seat  of  inoculation,  while  the 
plates  from  the  heart  and  organs  were  sterile. 

Case  II.     February  29th. — Harry  S ,  aged  two  ; 

intubation  ;  membranous  laryngitis  ;  recovery.  Clinical 
history  :  Admitted  with  marked  laryngeal  dyspnoea.  In- 
tubation gave  complete  relief.  No  membrane  visible 
anywhere  in  throat.  Very  slight  prostration.  Tempera- 
ture, 101°  F. ;  pulse,  124;  respiration,  32.  On  sixth 
day  tube  was  coughed  up.  Except  for  the  sHght  prostra- 
tion there  were  no  bad  symptoms. 

Bacterial  examination  :  Plates  and  tubes  made  from  a 
swab  of  the  throat  contained  a  number  of  typical  col- 
onies of  the  Klebs-Loeffler  bacilH.  Cultures  made  on 
following  days  gave  none.  Streptococci  were  always 
present.  Guinea-pig  died  in  forty-eight  hours  with  char- 
acteristic lesions. 

Case  III.     February  20th. — Sarah  S ,  aged  four  ; 

intubation ;  death.  Clinical  history :  The  child  had 
been  intubated  before  admission ;  heart  irregular  and 
weak ;  a  few  grayish  semi-adherent  patches  on  tonsils. 
Temperature,  100.6°  F.  ;  pulse,  134;  respiration,  42. 

February  2 2d. — Breathing  badly,  swallows  with  diffi- 
culty.    Died,  7.15  P.M. 

Bacterial  exammation  :  Plates  show  many  typical  col- 
onies of  Loeffler  bacilli,  and  many  of  streptococci. 

Case  IV.     February  23d. — Benjamin  J ,  aged  two 

years  and  ten  months  ;  intubation  ;  death ;  extensive  mem- 
brane. Chnical  history  :  Thick,  greenish-gray,  adherent 
pseudo-membrane  on  uvula,  anterior  faucial  pillar  and 
pharynx  ;  croupy ;  glands  of  neck  swollen.  Temperature, 
101°  F. ;  pulse,  126;  respiration,  38.     Very  restless. 

February  26th. — Intubated,  with  relief  of  laryngeal 
dyspnoea. 

February  27th.— Heart  failure  and  death. 

Bacterial  examination  :  Plates  revealed  a  great  number 
of  active  growing  colonies  of  the  Loeffler  bacilli,  and  some 
of  streptococci.  Guinea-pig  inoculated  died  between 
forty-eight  and  sixty  hours  with  characteristic  changes. 

Case  V. — Private  case,  aged  one  ;  intubation  ;  death ; 
extensive  membrane.  Clinical  history :  Soft,  gray- 
ish, pseudo  membranous  patches  on  tonsils,  base  of 
uvula,  and  in  nostrils.  Temperature,  101°  F. ;  pulse, 
120.  Membrane  spread  slowly  over  pharynx,  and  on 
fifth  day  invaded  the  larynx;  dyspnoea  gradually  in- 
creased ;  tissues  of  neck  became  greatly  swollen  ;  intu- 
bated with  but  slight  relief.  Died  on  seventh  day. 
Temperature  never  above  102°  F. 

Bacterial  examination  :  Many  colonies  of  the  Loeffler 
bacilli  and  of  streptococci. 

History  of  infection  :  Three  days  before  first  symp- 


1 8  DIPHTHERIA   AND   ALLIED 

toms  child  had  been  put  in  a  crib  for  a  few  hours,  occu- 
pied, two  weeks  before,  by  a  child  who  had  passed 
through  a  dangerous  attack  of  diphtheria. 

Case  VL     February  28th. — Rachel  M ,  aged  five. 

Death  after  disappearance  of  the  membrane.  Clinical 
history  :  Both  tonsils,  anterior  pillars,  left  side  of  uvula, 
and  soft  palate  covered  by  a  thick,  firmly  adhesive, 
grayish  pseudo  membrane.  Dirty  discharge  from  nose. 
Temperature,  99°  F. ;  pulse,  no;  respiration,  24. 
Apathetic. 

March  ist. — Croupy,  relieved  by  calomel  fumigation. 
Temperature,  99.5°  F. 

March  7th. — Thick  membrane  has  separated.  Super- 
ficial ulceration  on  faucial  pillars  and  tonsils  covered  by 
thick  purulent  discharge.  Since  the  third  the  urine  has 
contained  large  amounts  of  albumin.  Is  very  weak  and 
apathetic     Speaks  in  whispers  and  swallows  with  difficulty. 

March  15th. — Copious  discharge  continued,  and  patient 
seems  unable  to  swallow  or  spit  it  up.  Patient  suddenly 
began  to  breathe  with  feeble  gasps  and  died  at  7.30  a.m. 

Bacterial  examination  :  Cover  glass  frorn  smear  gave 
an  almost  pure  culture  of  typical  Loeffler  bacilli.  Cult- 
ures gave  a  large  number  of  colonies  of  the  Loeffler 
bacilli,  and  a  smaller  number  of  colonies  of  micrococci 
which  appeared  as  diplococci  and  in  rows  of  two  to 
eight.  After  the  disappearance  of  the  membrane  no 
more  Loeffler  bacilli  were  present,  the  micrococci  above 
noticed  and  many  other  forms  replacing  them. 

Guinea-pig  died  in  forty-eight  hours  with  characteristic 
lesions. 

Cases  7  to  10  in  one  family.     Malignant  diphtheria. 

Case  VIL  March  6th. — Cora  B ,  aged  twenty- 
six,  the  mother ;  died.  Clinical  history  :  Has  been  sick 
five  days.  Uvula,  posterior  fauces,  tonsils  and  pharjnx 
greatly  swollen  and  covered  by  a  very  thick,  yellow-gray 
membrane,  nostrils  occluded  by  membrane.  Lymph- 
glands  hard,  slightly  swollen.  Temperature  100.8°  F.  ; 
pulse,  106  and  feeble;  respiration,  26.  Is  apathetic,  can 
hardly  swallow  or  whisper.     Feels  that  she  is  choking. 

March  8th. — No  improvement.  Nasal  passages  ob- 
structed by  thick  membrane  ;  sweetish,  offensive  odor. 
Can  hardly  swallow  or  spit  up  the  copious  discharge. 
Patient  grew  worse  on  the  loth.  Pulse  became  imper- 
ceptible and  death  occurred  at  4  p.m. 

Case   VIII.     March    6th. — Maud   B ,  aged   five, 

daughter  of  last;  death  after  disappearance  of  mem- 
brane. Clinical  history  :  Sick  for  three  days.  At  base 
of  uvula  and  on  tonsils  are  large  patches  of  thick,  yellow- 
ish-gray pseudo-membrane.  Nasal  passages  occluded  by 
thick,  fibrinous  membrane.     Same  odor  as  from  mother. 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.        1 9 

Slightly  croupy.  Patient  seemed  at  first  to  do  well. 
The  membrane  gradually  separated,  and  on  the  nth  the 
throat  was  clear  of  membrane.  Some  ulceration  on 
fauces.  On  the  14th  began  to  vomit  food.  This  con- 
tinued on  15th.     Heart  became  weak  and  patient  died  at 

10  P.M. 

Case   IX. — Clifford   B ,  aged  one,   son  of  Cora 

B ;  died.    Clinical  history :  Sick,  three  days.    Pharynx, 

tonsils,  and  cavities  of  nose  lined  by  a  thick,  offensive,  ad- 
herent pseudo-membrane.  Croupy.  Patient  is  cyanotic 
and  septic,  and  very  restless.     Died  at  i.io  p.  m. 

Case  X. — George  B ,  aged  thirty  ;  father.  Clini- 
cal history  :  Has  had  for  one  day  sore  throat,  pains  in 
limbs,  and  prostration.  ^\Tiole  right  tonsil  is  covered  by 
a  thick,  soft,  grayish  smear,  which  can  easily  be  removed, 
leaving  adherent  follicular  deposits.  Slight  adherent 
patch  on  right  anterior  faucial  pillar. 

March  8th. — Merely  follicular  deposits  on  tonsil  and 
slight  membrane  on  anterior  pillar. 

March  14th. — Throat  clean,  except  small  patch  on 
right  anterior  pillar. 

March  17th. — Throat  clean.     Feels  well. 

Bacterial  examination  :  All  four  cases  gave  such 
typical  smears  on  cover-glasses  of  the  Loeffler  bacilli  that 
an  almost  certain  bacteriological  diagnosis  could  be 
immediately  made  of  true  diphtheria.  Besides  the 
Loeffler  bacilli,  all  had  many  colonies  of  a  streptococcus 
which  grew  rapidly  without  forming  looped  colonies.  In 
hanging  drop  it  grew  in  short  chains  and  as  diplococci. 
The  plates  showed  colonies  of  numerous  other  varieties 
of  cocci  and  bacilli. 

Guinea  pigs  were  inoculated  from  cultures  of  eight  and 
ten.  The  animals  died  in  seventy-two  and  twenty-four 
hours  with  characteristic  changes. 

The  history  of  the  spread  of  the  contagion  in  these 
cases  is  interesting.  Two  months  before,  a  child  living 
on  the  floor  below  them  had  what  the  doctor  called 
diphtheria.     Until  a   few   days   before   the    sickness   of 

Cora  B ,  the  two  families  had  kept  apart.     For  the 

last  few  days  they  had  visited  each  other,  and  Cora  had 
carried  and  played  with  the  child  who  had  recovered 
from  the  diphtheria.  "When  the  mother  took  sick  she  was 
still  allowed  to  nurse  and  carry  the  children.  Three  days 
later,  the  children  were  discovered  to  have  contracted  the 
disease.  The  mother,  too  sick  longer  to  nurse  the  chil- 
dren, confided  their  care  to  the  father,  who  himself 
became  infected.  Antiseptic  cleansing  of  the  nostrils  and 
throat  was  neither  used  in  treatment  nor  prophylaxis  in 
these  cases,  before  their  admission  to  the  hospital. 

Case  XL     February  23d. — Charles  B ,  aged  thirty; 


20  DIPHTHERIA   AND   ALLIED 

recovery.  Clinical  history  :  Both  tonsils,  faucial  pillars, 
and  base  of  uvula  are  covered  by  a  firmly  adherent,  thick 
pseudo-membrane  of  grayish  color.  Diffuse  infiltration 
of  adjacent  tissues  of  neck, 

February  24th. — Membrane  has  extended  forward  over 
palate. 

February  27th. — Membrane  separating  in  large  pieces. 

February  29th. — Clean,  except  for  superficial  ulcera- 
tion of  mucous  membrane  of  soft  palate. 

On  first  two  days  temperature  was  about  101°  F.,  after 
that  below  100°  F.  On  the  tenth  day  albumin  appeared 
in  the  urine. 

Bacterial  examination  :  Cultures  made  from  bits  of 
membrane  showed  many  colonies  of  the  Loefiier  bacilli, 
until  the  29th,  when  they  ceased  to  appear.  There  were 
always  many  colonies  of  the  streptococcus  present. 

Case  XII.  February  25th. — Gustav  V — — ,  aged 
twenty-one.  Recovery.  Clinical  history :  Thick  adherent 
patches  of  pseudo-membrane  on  tonsils  and  lateral  walls 
of  pharynx.  Membrane  began  to  peel  ofE  on  the  27th, 
and  had  all  disappeared  on  the  29th.  After  the  first  day 
the  temperature  was  normal.  Most  abundant  colonies 
are  of  the  Loeffier  bacilli ;  some  colonies  of  streptococci 
present.     After  the  29th  no  more  Loeffier  bacilli  present. 

Guinea-pig  inoculated  died  in  seventy  hours,  with  usual 
conditions. 

Case    XIII.      February    i6th. — Mary    C ,    aged 

twenty  ;  malignant ;  death.  Clinical  history  :  Has  been 
sick  two  days  before  admission.  Tissues  of  pharynx  and 
palate  swollen  and  oedematous.  Whole  of  uvula,  tonsils, 
part  of  soft  palate,  and  part  of  pharynx  covered  by  a 
thick,  adherent,  dirty  gray  pseudo-membrane.  Much 
swelling  of  tissues  of  neck.  The  breath  has  a  foul, 
sweetish  odor.  Patient  is  much  depressed.  Tempera- 
ture, 98°  F.;  pulse,  100;  respiration,  28.  The  pharynx, 
tonsils,  and  soft  palate  became  one  swollen  mass  covered 
by  sloughing  membrane.  Swallowing  difficult.  For  the 
last  two  nights  patient  was  delirious  and  restless. 

February  20th. — Pulse  became  rapidly  weaker,  and 
death  occurred.  Bacterial  examination  :  Plates  showed 
many  varieties  of  bacteria,  of  which  the  Loeffier  colonies 
comprised  about  one-third.  Streptococci,  micrococci, 
and  bacilli  were  present. 

Case  XIV.     March  24th. — Polly  K ,  aged  thirty  ; 

malignant ;  recovered.  Clinical  history  :  Sick  two  days. 
Pharynx,  tonsils,  and  soft  palate  swollen  and  oedematous. 
Tonsils,  faucial  pillars,  and  part  of  soft  palate  covered 
by  a  rotten,  grayish-green,  adherent  pseudo-membrane. 
Great  prostration.  Temperature,  101.4°  F.;  pulse,  100; 
respiration,  20. 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.        21 

March  25th. — Condition  unchanged.  Temperature, 
99.4°  F. 

March  29th. — Membrane  nearly  disappeared.  Condi- 
tion improved.  Three  children  of  this  patient  died. 
Bacterial  examination  :  Many  colonies  of  the  Loeffler 
bacilli,  many  of  the  streptococci  and  others. 

Case  XV. — Child,  aged  six  weeks  ;  death  ;  private 
practice.  Clinical  history  :  On  first  day  small  adherent 
patch  on  left  tonsil  and  on  base  of  uvula,  also  a  piece  of 
membrane  hanging  down  from  naso-pharynx,  membrane 
spread  over  pharynx,  and  on  third  day  into  larynx. 
Child  died  on  the  fifth  day.  Glands  were  never  swollen, 
and  temperature  did  not  rise  above  99°  F.  until  a  few 
hours  before  death.  The  day  before  the  illness  of  the 
chDd  was  noticed  the  mother  was  discovered  to  have 
diphtheria,  and  the  child  immediately  removed,  but  too 
late.  The  mother  went  through  a  severe  illness,  also 
without  fever,  but  recovered.  Bacterial  examination  : 
An  almost  pure  culture  of  Loeffler  colonies  on  plates. 
No  streptococci. 

Animal  inoculation  :  Guinea-pig  died  in  fifty  hours, 
with  fairly  characteristic  lesions. 

Case  XVI. — Child,  aged  two ;  recovery.  Clinical 
history  :  Adherent  gray  patches,  first  on  tonsils,  then  on 
pharynx  and  roof  of  soft  palate.  On  seventh  day  spread 
to  larynx  and  caused  great  dyspnoea.  Calomel  fumiga- 
tions given  every  hour.  Child  never  seemed  very  ill, 
except  for  the  dyspnoea.  Temperature  never  above 
100°  F.     Glands  not  swollen. 

Bacterial  examination  :  The  majority  of  the  colonies 
were  those  of  the  Loeffler  bacilli.  Numerous  colonies  of 
micrococci  were  also  present.     No  streptococci  found. 

Case  XVII.  February  13th. — Child,  aged  six  ;  pri- 
vate practice ;  recovered.  Clmical  hi^'tory  :  When 
first  seen  tonsils  were  swollen.  Next  day  adherent 
patches  seen  on  tonsils.  Tonsils  became  clean  five  days 
later.  Some  days  afterward  child  was  noticed  to  limp, 
and  slight  paresis  of  muscles  of  left  side  was  found.  In 
the  next  house,  the  week  before,  there  was  a  case  of 
clinical  diphtheria,  and  this  child  played  with  the  children 
from  the  other  house. 

Bacterial  examination  :  Many  colonies  of  Loeffler  ba- 
cilli and  many  scattering  forms. 

Case   XVIII.      April    25th.  —  Minnie    M ,    aged 

twelve.  Abscess  tonsil ;  diphtheria.  Comes  from  an 
asylum  from  which  three  others  with  diphtheria  have 
been  received.  Has  complained  of  sore  throat  for  two 
days.  Both  tonsils  and  left  peritonsillar  region  swollen 
and  hyperaemic.  Adherent  patches  on  left  tonsil,  fol- 
licular deposits  on  right.     Temperature,  102°  F.  ;  pulse 


22  DIPHTHERIA   AND   ALLIED 

90  ;  respiration,  24.  Abscess  in  left  tonsil  ruptured  and 
discharged  a  large  amount  of  pus  at  the  moment  of  ex- 
amination. Recovered  entirely  by  fourth  day.  Cultures 
gave  numerous  colonies  of  the  Klebs  Loefifler  bacilli  and 
of  long-chained  streptococci. 

Guinea-pig  inoculated  died  in  forty-four  hours,  with 
characteristic  lesions.  Plates  and  tubes  from  tissue  at 
point  of  inoculation  gave  abundant  colonies. 

Case  XIX.  February,  1892. — Child,  aged  six  weeks; 
private  practice  ;  death.  Chnical  history  :  Began  with 
bloody  discharge  and  membrane  in  nose.  Membrane 
spread  to  pharynx,  tonsils,  and  larynx.  Death  about  the 
tenth  day.  Father  of  child  had  been  attending  diphtheria 
cases. 

Bacterial  examination  :  Cultures  from  a  piece  of  mem- 
brane gave  abundant  colonies  of  the  Loefifler  bacilli  and 
of  the  long-chained  streptococcus.  A  piece  of  mem- 
brane taken  three  days  later  from  the  nose  gave  very 
numerous  colonies  of  the  staphylococcus  pyogenes  aureus. 
Guinea-pig  died  in  forty-eight  hovus,  with  characteristic 
lesions,  after  inoculation  with  the  bacilli. 

Case  XX.  February  13th. — Henry  K ,  aged  six- 
teen. Clinical  history  :  For  one  week  a  room-mate  had 
been  sick  with  diphtheria,  swabs  from  whose  throat  gave 
an  almost  pure  culture  of  the  Klebs  Loeffler  bacilli.  On 
first  day  of  his  illness  both  tonsils  and  adjacent  borders 
of  pillars  were  covered  by  a  thick,  soft,  dirty  pseudo- 
membrane.  The  pharynx  and  fauces  were  swollen  and 
deeply  injected.  Temperature,  103°  F. ;  pulse,  120. 
Glands  swollen. 

February  14th. — The  tonsils  still  swollen  and  painful, 
but  the  diffuse  membrane  disappeared,  leaving  only 
croupous  patches  confined  to  the  tonsils. 

February  17th. — Small  follicular  deposits  still  remain. 

February  i8th. — Tonsils  clean,  though  still  swollen. 

There  was  never  any  albumin  in  urine.  Temperature 
and  pulse  sank  to  normal  on  the  second  day. 

Bacteria]  examination  :  Very  numerous  colonies  of  the 
Loeffler  baclli,  some  streptococci. 

Case   XXI.      March    23d. — Cornelius   V ,    aged 

seven.  Clinical  history :  Tonsils,  anterior  faucigl  pillars, 
and  roof  of  soft  palate  covered  by  a  thick,  grayish-white, 
adherent  membrane.  Temperature,  101°  F.;  pulse,  120. 
Marked  swelling  in  adjacent  tissues  of  neck.  Consider- 
able prostration. 

March  27th. — Membrane  peeling  off.  Glands  of  neck 
less  swollen.  Temperature,  100°  F,;  pulse,  130,  Pros- 
tration still  marked. 

March  29th. — Expelled  a  large  piece  of  membrane  from 
nose. 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.       23 

April  I  St. — Throat  clear.  Temperature,  98.6°  F.; 
pulse,  130.     Made  a  slow  recovery. 

Bacterial  examination  :  Very  abundant  colonies  of 
Loeffler  bacilli  and  many  streptococci. 

Case  XXII.     March   23d. — John    V ,  aged  five, 

brother  of  previous  case.  Clinical  history  :  Slight  ad- 
herent patch  on  left  tonsils.  Hardly  complains  at  all. 
Temperature,  100°  F. 

Mirch  25th. — Patch  smaller. 

March  27  th. — Throat  clean.     Feels  well. 

Bacterial  examination  :  Cover-glasses  show  many  typi- 
cal Loeffler  bacilli,  of  chain  cocci  and  diplococci.  The 
cultures  from  both  cases  contained  many  colonies  of  the 
Loeffler  bacilli,  streptococci,  and  micrococci. 

The  previous  week  the  oldest  sister  had  croupous  in- 
flammation of  the  tonsils  and  soft  palate.  The  children 
were  not  isolated.  The  second  child  had  absolutely  no 
symptoms.  Treatment  with  spray  and  douche  of  i  to 
4,000  bichloride  solution  was  begun  probably  a  few 
hours  aft^r  infection. 

Case  XXIII.     February  17th. — Gussie  G ,  aged 

three  and  a  half ;  diphtheritic  rhinitis ;  recovery. 
Clinical  history  :  Slight  deposits  on  left  tonsil.  Obstruc- 
tion to  nasal  breathing  and  dirty  discharge  from  the  nose. 

February  21st. — Small  adherent  patches  still  on  ton- 
sils.    Glands  on  left  side  of  neck  swollen  and  painful. 

February  23d. — Today  a  large,  thick,  fibrinous  pseudo- 
membrane,  four  inches  in  length,  was  washed  from  the 
nose.  It  was  a  partial  cast  of  both  nostrils.  Patient 
doing  well.     Tonsils  almost  clean. 

On  the  25th  scarlet  fever  developed,  from  which  she 
finally  recovered.  Temperature  never  rose  over  101°  F. 
until  the  development  of  the  scarlet  fever. 

Bacterial  examination  :  From  the  pharynx  the  culture 
showed  many  typical  colonies  of  the  Klebs-Loeffler  ba- 
cilli. From  the  membrane  from  the  nose  only  a  very 
few  colonies  were  obtained,  among  which  were  a  few  of 
the  Krebs- Loeffler  bacilli  and  a  few  of  the  streptococci. 

Membranous  Rhinitis. — Case  I. — January  19,  1892. 
Roosevelt  Dispensary.  Service  Dr.  Jonathan  Wright. 
Aged  three.  Recovery.  Clinical  history  :  Right  nostril 
occluded  by  a  thick  succulent  membrane.  Left  shows  in 
front  small  adherent  deposits.  Upper  lip  eczematous  with 
a  few  pustules.  Bloody  secretion  from  nose.  Pharynx 
and  larynx  free.  Temperature  by  rectum,  100°  F,;  pulse, 
rapid.  Removal  of  a  piece  of  membrane  caused  consid- 
erable bleeding.  Patient  never  seemed  really  ill.  On  the 
fifth  day  the  nostrils  were  free  from  membrane.  Still 
considerable  discharge  and  swelling.    No  albumin  in  urine. 

Bacterial  examination  :  Cover  glass  preparations  from 


24  DIPHTHERIA   AND   ALLIED 

membrane  showed  cocci,  diplococci,  and  bacilli,  among 
which  were  some  fairly  typical  Loeffler  bacilli.  Cultures 
contained  numerous  colonies  of  Loeffier  bacilli  and  of  the 
long- chained  streptococci  and  of  a  few  other  micrococci. 

Guinea-pig  inoculated  with  i  to  2  c.c.  of  bouillon  cult- 
ure, second  generation,  of  the  Loeffler  bacilli,  died  on 
the  fifth  day,  with  characteristic  lesions.  A  rabbit  was 
inoculated  in  the  ear  with  i  to  2  c.c.  of  a  bouillon 
culture,  two  days  old,  of  the  streptococci.  On  the  sec- 
ond day  rabbit's  temperature  was  102^  F.;  the  ear 
about  inoculation  somewhat  reddened.  On  third  day 
temperature  103°  F.,  considerable  redness  and  cedema  of 
the  whole  central  half  of  ear  was  present.  The  temper- 
ature and  local  signs  of  inflammation  then  subsided. 

Case    II. — Gertrude   B ,  aged  four.      Discharge 

and  occluded  nostrils  for  six  days;  peevish;  ansemic. 
Both  nostrils  filled  in  front  by  a  thick,  succulent,  adherent, 
light-gray  membrane.  Free  hemorrhage  on  removal. 
Pharynx  clear  of  deposit.  Temperature,  pulse,  and  res- 
piration nearly  normal.  Urine,  1.007,  dear,  no  albumin 
or  casts.     On  sixth  day  membrane  separated. 

Case  III. — Tom  Mc :,  aged  four  and  a  half.     Van- 

derbilt  Clinic,  service  Dr  Simpson.  Discharge  and  oc- 
cluded nostrils  one  week.  Both  nostrils  filled  by  thin, 
grayish- white,  adherent  pseudo-membrare.  Tempera- 
ture, 100°  F.;  pulse,  130.  Urine,  i. 010,  clear;  no  albu- 
min or  casts.     Nostrils  clear  sixth  day. 

Case  IV. — Ellen  B ,  aged  eighteen  months.  Roose- 
velt Dispensary.  For  six  weeks  has  had  an  otitis  media. 
For  one  week  discharge  from  nose.  On  septum  and  tur- 
binated bones  thin,  grayish-white,  adherent  membrane. 
Child  seeras  well.    Membrane  all  disappeared  on  fifth  day. 

Case  V, — E.    W ,    aged   five.     Same    history    as 

previous  cases.  Membrane  separated  sixth  day.  Never 
appeared  sick. 

Case  VI. — Mary  B ,  aged  three.  Membrane  sep- 
arated sixth  day.     Never  appeared  seriously  ill. 

In  all  the  latter  five  cases  of  membranous  rhinitis  quite 
numerous  colonies  of  the  Klebs-Loeffler  bacilli  were 
present,  in  three  associated  with  streptococci,  and  in  two 
with  staphylococci.  From  the  first  four,  guinea  pigs 
were  inoculated.  One  died  on  the  fifth  day  and  one  on 
the  seventh.  The  other  two  appeared  sick  for  a  few  days 
and  then  recovered.  In  the  neighborhood  of  the  inocula- 
tion some  induration  could  be  felt.  The  slight  virulence 
of  the  bacilli  is  remarkable. 

These  cases  are  very  interesting.  Like  those  observed 
by  all  other  observers  they  ran  a  benign  course.  The  only 
precaution  to  prevent  the  spreading  of  the  contagion  was 
antiseptic  irrigation.     No  history  of  infection  was  ob- 


PSEUDO-MEMBRANOUS   INFLAMMATIONS. 


25 


tained  in  any.  In  all  six  cases  the  colonies  of  the  Loeffler 
bacilli  grew  rather  feebly,  both  on  the  blood-serum  and 
on  the  agar.  The  bacilli  from  the  agar  were  small  and 
often  pomted,  from  the  blood-serum  and  broth  long  and 
slender,  with  swollen  ends.  The  cultures  died  out  more 
quickly  than  those  from  ordinary  cases.  The  bacilli  in 
the  membrane  were  rather  long  and  slender,  with  few 
clubbed  forms. 


Cases  of  Laryngeal  Diphtheria  Requiring  Intubation. 


Name. 


Age. 


oi"^   C    in 
"    C    2-- 

s. "'  s- « c 

u   P<  iH   O   in 
H 


Result. 


'Lizzie  D . . 
Maggie  D . 

Margt.  G. 
Lena  G. . . 

Abram  A. . 


6   Ike  S 

71  Charles  H. 

8  Female  . . . 

9  Female  . . . 


4yrs. 

I  yr. 
4>^yrs. 

2>^yrs. 


4yrs. 

syrs. 

Syrs. 

2yrs. 
4yrs. 
2}^  yrs. 

I  yr. 


Croupous  laryn- 
gitis. 

Croupous  laryn- 
gitis :  slight 
patches  ton- 
sils. 

Croupous  laryn- 
gitis ;  tonsils 
and  uvula. 

Croupous  laryn- 
gitis ;  si  i  ght 
patches  ton- 
sils. 

Croupous  laryn- 
gitis ;  tonsils. 
Pneumonia  ? 


Temp.,  102  ; 

pulse,  130 ; 

rasp.,  40. 
T  e  m  p  e  ra- 

ture,  101.6  ; 

pulse,  118  ; 

resp.,  28. 
Temp.,  10 1  ; 

pulse,  150 ; 
•  resp.,  56. 
Temp.,  102  ; 

pulse,  140; 

resp.,  42. 

Temp.,  104; 
pulse,  136 ; 
resp.,  46. 


Croupous  laryn-  Temp.,  100  ; 


gitis ;  bron 
chitis. 

Croupous  laryn- 
gitis ;  scarlet 
fever. 

Croupous  laryn- 
gitis ;  m  e  a  - 
sles. 

Croupous  laryn- 
gitis ;  tonsils 
and  pharj-nx. 

Croupous  laryn- 
gitis; slight 
patches  ton- 
sils. 

Croupous  laryn- 
gitis. 

Croupous  laryn- 
gitis. 

Croupous  laryn- 
gitis ;  pharynx 
and  tonsils. 

Croupous  laryn- 
gitis ;  pharynx 
and  nostrils. 


pulse,  132  ; 

resp.,  30. 

;Temp.,  103. 


Reported 

in  his- 

\-  tories     of 

Cases 

No.  1-5. 


Intubated  3d 
day ;  died 
4th  day. 

Intubated  be- 
fore    admis- 


Tntubated     4th 

day  ;    died 

6th  day. 
Intubated     4th 

day ;     died 

6th  day 


Intubated     be-  1  Died, 

fore     admis-  I 

sion  ;    died 

next  day. 
I  n  t  ubated   on 

admission. 


Died. 
Died. 

Died. 
Died. 


Recov- 
ered. 


I  n  t  u  bated  on 
admission. 


Intubated 


Intubated  '. , 
Intubated  . . 


Intubated  . 
Intubated  . . 
Intubated  . . 


Intubated 


Recov- 
ered. 

Recov- 
ered. 

Died. 
Died. 

Recov- 
ered. 
Died. 

Died. 
Died. 


Whole  number  of  cases  requiring  intubation,  14,  of  which  10  died  and  4  recov- 
ered. Ages  varied  between  one  and  five  years.  In  Case  8  the  bacilli  grew  and 
appeared  like  those  in  the  membranous  rhinitis  cases.  In  6  of  these  no  membrane 
was  visible  anywhere  above  the  larynx.  In  i  scarlet  fever,  and  in  i  measles  ex- 
isted as  a  complication. 


26 


DIPHTHERIA   AND    ALLIED 


Table  of  Diphtheria  Cases  not  Included  in  the  List  of 
Cases  of  Mejnbranous  Rhinitis  and  Laryngitis. 


Age. 

Location  of  Pseudo-membrane. 

s 

3 

Tonsils. 

Oi 

Nose  and  phar- 
ynx. 

X 

a 
>. 

S  , 
i-l- 

B 

3 

Q 

Result. 

I 
2 

3 

4l 

s' 

6 

F. 

M. 
F. 
F. 
F. 
F 

6  years. 

4  years. 
6  years. 

12  years. 
10  years. 

4  years. 

4  years. 

Follicular  de- 
posits. 

Patches 

Patches 

Patches 

l*  ollicular  .    . . 

Patches 

Patches 

Patches 

Patches 

Patches 

Patches 

Patches   

Deposits  .... 
Follicular  .... 

Patches 

Follicular 

Extensive  .... 
Extensive..  . . 

Extensive 

Extensive 

Extensive . .  . 

Extensive 

Extensive. .  . . 
Extensive .... 
E.xtensive .... 

Slight 

Slight 

Slight 

Slight 

Extensive. .  . . 
Extensive . . . 
Extensive. . . . 

Slight 

Slight 

I 

I 

Days. 
6 

4 
4 
4 
5 
4 
4 
5 
6 
5 
4 
6 
5 
8 

Recovered. 

Recovered. 

Died. 

Recovered. 

Recovered. 

Died. 

7i  M. 
8   F. 

Died. 

g;  B'.    1    6  years, 
lo;  v.    •  IS  years. 
II    F.      i6  years. 
12,  M.     21  years. 

13  F.        4  years. 

14  F.    I    6  years. 

I 

Died. 

I 

•• 

Died. 
Recovered. 

Recovered. 

16 
17 
18 
19I 
20 
21 
22 
23 
24 
25 
26 
27 

F. 

4  years. 

5  years. 
26  years. 

5  years. 
I  year. 

30  years. 

30  years. 

21  years. 
i  20  years. 

30  years. 
i    6  weeks. 
j    2  years. 
I    6  years. 
Syear.s. 

6  weeks. 
16  years. 

7  years. 
S  years. 

5  months. 

I 
I 
I 
I 

I 

Ptiarynx 

Naso-pharynx. . 

I 
I 

I 
I 

1 

8 
15 
7 
9 
4 
10 
6 
4 
6 
7 
5 

Died. 

Died. 

Died. 

Died. 

Died. 

Recovered. 

Recovered. 

Recovered. 

Died. 

Recovered. 

Died. 

Recovered. 

29 
30 
31 
32 
33 
34 

I 

Recovered. 

Died. 

Died. 

Naso-pharynx. . 
Naso-pharynx . . 

I" 

Recovered. 
Recovered. 
Died. 

Resume  of  Points  of  Interest  in  the  Fifty -four  Cases  of 
True  Diphtheria.  (The  reliability  of  cultures  and  of 
the  immediate  diagnosis  from  cover  glass  smears.) — In 
every  case  in  which  cultures  revealed  the  Loeffler  bacilli 
during  any  part  of  the  disease  the  first  examination  dis- 
closed numerous  colonies.  This  would  seem  to  show 
that  cultures  made  from  a  fresh  swab,  or  bit  of  mem- 
brane, can  be  thoroughly  relied  upon  to  show  the  presence 
or  absence  of  the  Loeffler  bacilli  as  soon  as  the  pseudo- 
membrane  is  developed.  After  the  complete  separation 
of  the  membrane  they  were  in  every  case  missed.  In 
many  cases  an  examination  of  cover-glass  smears,  when 
made  from  fresh  swabs  or  membrane,  gives  an  immediate 
reliable  diagnosis.  This  requires  great  care  and  should 
always  be  controlled  by  cultures.  Swabs  from  the 
pharynx  of  cases,  in  which  no  membrane  was  visible,  also 
give  knowledge  of  the  bacteria  infecting  the  larynx. 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.        2/ 

Methods  of  Spreading  the  Contagion. — Cultures  made 
from  the  dried  stains  on  spreads,  pillow-ca'^es,  and  sheets, 
where  soiled  by  the  expectoration  of  diphtheria  patients, 
showed,  in  every  case,  at  least  a  few  colonies  of  the 
Loeffler  bacilli.     (See  Photograph  4.) 

We  know  by  actual  experiment  that,  under  favorable 
conditions,  when  mixed  with  shreds  of  tissue  and  mu- 
cus, they  live  for  many  weeks.  The  sputum  of  patients, 
though  apparently  not  containing  any  bits  of  membrane, 
is  yet  usually  crowded  with  them. 

More  than  one  third  of  the  cases  gave  a  clear  history 
of  having  been  brought  in  contact  with  the  persons  or 
clothes  of  those  suffering  from,  or  having  recently  had, 
severe  pseudo  membranous  inflammations,  diagnosed  as 
diphtheria ;  and  in  eight  the  diagnosis  had  been  verified 
by  finding  the  Loeffler  bacilli. 

Case  V.  brings  out  strongly  the  manner  in  which  diph- 
theria breaks  out  in  unexpected  places.  The  child,  aged 
five,  is  taken  out  of  town  and  left  to  sleep  in  an  infected 
bed  for  a  few  hours,  and  dies  ten  days  later.  In  another, 
a  child  is  sent  away  for  safety,  but  carries  with  him  his 
infected  clothes,  and  some  of  his  playmates  take  the  dis- 
ease and  die,  while  he  himself  escapes. 

In  another,  five  weeks  before  there  existed  diphtheria 
in  the  flat  below.  The  first  new  patient  taken  sick  was  a 
child,  aged  two  and  a  half  years,  three  days  later  another, 
aged  four,  and  then  the  mother  herself.  The  children 
died,  the  mother  went  to  the  hospital  and  finally  recov- 
ered. When  she  left  home,  her  seven  months'  baby  went 
to  a  friend's,  where,  three  days  later,  two  of  the  children 
developed  diphtheria,  and  then  finally  the  baby  itself. 
The  baby  came  to  the  hospital  and  died,  one  of  the  other 
children  died. 

Cases  VII.  to  X.  show  the  methods  of  transmitting  the 
disease  from  one  to  the  other.  The  sick  mother  carries 
the  children  and  infects  them.  The  father  cares  for 
them  and  is  himself  infected. 

Physicians  certainly  are  not  careful  enough  to  avoid 
carrying  infection  in  their  clothing,  and  to  make  sure 
that  those  whom  they  send  from  an  infected  house  do 
not  take  it  with  them.  In  several  of  those  in  which  the 
history  of  infection  was  investigated,  great  carelessness 
on  the  physician's  part,  in  regard  to  warning  those  about 
the  sick,  was  shown.  The  large  number  of  cases  of  diph- 
theria which  occur  in  the  families  of  physicians  should 
lead  them  to  realize  the  danger  of  their  carrying  infection 
to  others. 

The  practice,  in  hospitals  for  contagious  diseases,  of 
wearing  gowns  when  examining  patients,  should  be  par- 
tially adopted  by  practitioners.     The  frequent  crowded 


28  DIPHTHERIA   AND   ALLIED 

condition  of  the  diphtheria  wards  in  the  hospital  forces 
the  placing  in  the  same  room,  and  often  in  adjacent  beds, 
those  having  true  diphtheria  and  those  not  having  it. 

At  first  it  would  seem  that  the  contagion  must  be  car- 
ried from  one  to  the  other,  but,  as  far  as  the  Resident 
Physician  knows,  this  has  not  taken  place  in  the  last  two 
years,  and  it  certainly  never  occurred  during  these  inves- 
tigations. 

The  great  attention  paid  to  cleanliness  in  the  wards 
and  the  sterilization  of  instruments  of  examination  ac- 
count partly  for  this,  but  the  routine  cleansing  of  the  nos- 
trils and  throats  of  all  patients  with  a  weak  bichloride 
of  mercury  solution  has  also  an  important  share  in  giv- 
ing this  freedom  from  infection.  The  iiiportant  fact  is 
that  it  seems  possible  to  almost  entirely  prevent  the  spread 
of  diphtheria  if  proper  precautions  are  taken. 

Age. — Of  the  54  cases,  43  were  under  10  years;  2 
were  under  8  weeks  ;  1 1  were  adults. 

Mortality. — Twenty-five  died  out  of  the  54  ;  4  deaths 
occurred  in  the  11  adults;  10  of  the  14  cases  requiring 
intubation  died. 

Effect  of  Treatment. — The  patients  that  died  in  the 
hospital  were,  without  exception,  those  that  on  admission 
had  either  very  extensive  membrane  or  laryngeal  compli- 
cations. In  only  three  was  there  any  extension  of  the  dis- 
ease after  irrigation  with  i  to  4,000  bichloride  solution 
had  been  commenced.  In  a  number  of  families  where 
different  members  had  had  the  disease  for  different 
lengths  of  time,  those  longest  sick  without  treatment  did 
badly,  while  those  just  attacked  did  very  well.  In  these 
cases  the  virulence  of  the  bacilli  and  the  family  predis- 
position were  the  same  in  both  the  early  and  later  cases, 
so  that  the  great  difference  in  the  course  of  the  disease 
in  the  two  classes  was  probably  the  effects  of  the  treat- 
ment. 

Location  of  Pse ado-membrane. — Of  the  54  cases,  in  6 
the  disease  was  confined  to  the  nostrils,  in  5  to  the  larynx 
and  bronchi.  In  all  others  the  tonsils  were  more  or  less 
involved.  In  bad  cases  the  soft  palate  and  uvula  were 
extensively  invaded.  In  the  adults,  the  pseudo- membrane 
was  generally  thick,  usually  extensive,  and  of  a  dirty 
grayisji  color.  In  bad  cases,  the  membrane  became  very 
thick  and  offensive.  In  some  of  the  children  the  mem- 
brane presented  the  same  appearance  as  in  adults,  while 
in  others  it  was  thin  and  grayish  white,  often  simply  in 
the  form  of  little  patches  on  the  tonsils,  uvula,  soft  palate, 
or  faucial  pillars. 

Two  cases  with  true  diphtheria  from  an  asylum,  one 
appearing  like  a  follicular  tonsillitis  and  the  other  with 
an  abscess  of  the  tonsil,  bring  out  the  difficulty  in  making 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.        29 

a  clinical  diagnosis.     In  most  of  the  mild  cases  in  chil- 
dren this  was  impossible. 

The  severity  of  the  disease  seems  to  be  almost  directly 
in  proportion  to  the  extent  of  the  membrane.  The  dif- 
ference in  cases  is  very  striking.  Those  of  croupous  rhi- 
nitis, and  many  in  which  the  disease  is  confined  chiefly  to 
the  tonsils  and  uvula,  both  children  and  adults,  hardly 
seem  ill  at  all.  Others  with  throat  and  nose  lined  with 
membrane  are  very  seriously  ill  from  the  beginning  and 
usually  die. 

The  cause  of  the  great  difference  in  these  cases  is  a 
very  interesting  study.  It  is  certainly  true  that  malignant 
cases  usually  propagate  malignant  ones,  and  mild  cases 
mild  ones.  It  is  also  true  that  now  and  then  a  severe 
case  has  received  its  infection  from  a  mild  one,  and  more 
frequently  still,  mild  cases  have  come  from  severe  ones. 

The  most  plausible  explanation  seems  to  be  that  there 
is  a  great  difference  in  the  virulence  of  bacilli  from  dif- 
ferent cases,  and  also  that  the  degree  of  susceptibility  of 
individuals  varies  greatly.  Some  seem  almost  to  be  im- 
mune. Whether  the  greater  proportion  of  children  in- 
fected is  due  to  their  greater  susceptibility,  or  to  the  fact 
that  they  are  so  apt  to  put  things  in  their  mouths,  and 
that,  when  carried,  their  faces  are  brought  directly  against 
that  portion  of  the  clothing  most  likely  to  be  infected,  is 
an  interesting  question. 

In  the  limited  number  of  cases  here  examined  the  ef- 
fect of  the  association  of  other  organisms  cannot  be  safely 
judged.  The  opinion  has  been  forced  strongly  upon  me 
that  the  Loeffler  bacillus  is  the  predominating  factor. 
Some  of  those  having  given  pure  cultures  of  the  Loef- 
fler bacilli  have  been  fatal,  while  others  in  which  strepto- 
cocci abounded  have  been  very  mild.  In  malignant 
cases  with  sloughing  membrane  the  surface  is  crowded 
with  micrococci  and  bacilli,  but  the  probability  is  that 
they  find  the  dead  tissue  a  good  soil  for  their  growth.  In 
small  children  the  association  of  the  streptococci  probably 
adds  to  the  danger  of  a  complicating  broncho-pneumonia. 

The  temperature  has  been  looked  upon  as  a  test  by 
some.  It  is  the  general  experience  of  those  who  have 
inoculated  animals  with  Loeffler  bacilli  that  the  temper- 
ature falls  soon  after,  and  remains  subnormal  till  death. 
On  the  other  hand,  inoculations  of  streptococci,  when 
they  produce  any  effect,  raise  the  temperature. 

In  those  cases  of  diphtheria  in  which  the  bacilli  alone 
were  present  the  temperature  never  rose  above  100°  F. 
In  those  in  which  the  streptococci  were  abundant  some 
had  a  high  temperature,  others  a  low.  For  prognosis  the 
temperature  was  of  no  value  except  in  children  where 
lung  complications  occurred. 


30  DIPHTHERIA   AND   ALLIED 

The  marked  swelling  of  the  cervical  glands  and  tissues 
was  present  only  in  those  cases  where  other  bacteria,  es- 
pecially streptococci  were  present.  In  many  fatal  cases 
there  was  no  swelling,  while  some  in  whom  it  was  marked 
recovered.  In  the  bad  cases,  albumin  in  large  amounts 
usually  appeared  in  the  urine.  In  many  mild  cases,  no 
albumin  was  ever  found.  The  deaths  occurring  some 
days  after  all  membrane  had  disappeared  from  the  throat 
bring  out  a  peculiar  danger  in  diphtheria. 

The  six  cases  of  membranous  rhinitis  are  of  great 
interest,  for  it  is  only  very  recently  that  they  have  been 
thought  to  have  any  relation  to  true  diphtheria.  They 
seem  regularly  to  recover. 

Pseudo-membraiious  Inflammations  in  which  the  Klebs- 
Loeffler  Bacilli  are  Never  Present. — These  will  be  con- 
sidered in  the  following  clinical  divisions:  i.  Extensive 
pseudo  membranes,  mostly  confined  to  tonsils,  soft  palate, 
and  pharynx :  a.  Uncomplicated  ;  ^,  complicating  infec- 
tious diseases.  2.  Pseudo-membranes  involving  larynx 
(as  only  two  of  these  were  complicated  by  infectious  dis- 
eases they  will  be  considered  with  the  uncomplicated 
cases).     3.  Pseudo-membranes  confined  to  the  tonsils. 

Extensive  Pseudo  7nembranes,  Confined  Chiefly  to  the 
Tonsils,  Soft  Palate,  and  Pharynx. — Case  I.     February 

5,   1892. — Polly   D ,  aged  eight.     Clinical  history  : 

Tonsils  covered  by  large,  irregular,  adherent,  whitish 
patches.  Fauces  and  tonsils  swollen,  and  livid  in  color. 
Temperature,  104°  F.;  pulse,  40;  respiration,  20. 

February  6th. — Tonsils,  sides  and  tip  of  uvula,  and 
faucial  pillars  covered  by  a  thin,  friable,  grayish  pseudo- 
membrane,  which  leaves  a  bleeding  surface  on  removal. 
The  appearance  is  as  if  on  a  mucous  membrane  denuded 
of  its  superficial  epithelium  a  thick  paint  had  been  ap- 
plied. 

February  7th. — Tonsils  and  faucial  pillars  clear  of 
membrane  ;  superficial  ulceration  on  pillars,  and  adher- 
ent membrane  to  uvula.  Temperature  remains  between 
102  and  104°  F.;  pulse,  118  to  130;  respiration,  24  to 

30- 

February   i6th. — Ulceration   on  uvula  nearly  healed. 

Temperature  normal.     No  albumin  in  urine  at  any  time. 

No  great  prostration. 

Bacterial  examination  :  Cultures  were  made  daily  from 
bits  of  membrane  or  swab,  but  never  revealed  any  Loef- 
fier  bacilli.  A  quick-growing  streptococcus  which  often 
appeared  as  a  diplococcus  was  always  the  most  frequent 
organism  present. 

Case    II.     February    27th. — Charlotte   V ,    aged 

nineteen.     Clinical  history  :  Both  tonsils,  and    adjacent 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.        3 1 

surfaces  of  uvula  covered  by  a  thin  gray  membrane. 
Tonsils  much  swollen  and  painful.  Great  hypersemia  of 
pharynx.  Temperature,  99.6°  F.;  pulse,  100.  No  al- 
bumin in  urine. 

February  29th. — All  symptoms  abated.  Membrane 
disappeared.     No  sw^elling  of  glands. 

Bacterial  examination  :  Almost  pure  culture  of  strep- 
tococci growing  in  long  twisted  chains. 

Case  III.     February  3d. — Rose  L ,  aged  sixteen 

months.  Clinical  history  :  Thin,  adherent,  serai-trans- 
lucent membrane  on  tonsils  and  adjacent  surfaces  of 
uvula.  Nostrils  occluded,  but  no  membrane  visible. 
Croupy  voice  and  breathing.  Slight  swellmg  of  glands 
of  neck.  Temperature,  100.2°  F.;  pulse,  136;  respira- 
tion, 34. 

February  4th. — Membrane  nearly  disappeared.  Child 
nearly  well. 

February  6th. — Throat  perfectly  clean.  Child  is  well. 
Evening  temperature,  100°  F.;  pulse,  118  j  respiration,  28. 

Bacterial  examination  :  Almost  pure  culture  of  a 
streptococcus  growing  in  long  chains.  A  few  colonies  of 
a  short-chain  bacillus. 

Case   IV.     March  14th. — George  M ,  aged  four 

years.  Clinical  history  :  Five  days  ago  both  tonsils  re- 
moved. Now,  on  depressed  stumps  of  tonsils,  on  an- 
terior pillars,  and  on  adjacent  surfaces  of  the  uvula  is  a 
very  thin  grayish  membrane.  Complains  of  sore  throat 
and  not  feeling  well. 

March  8th. — Membrane  has  disappeared. 

Bacterial  examination  :  Plates  and  tubes  gave  a  pure 
culture  of  a  rapid-growing  streptococcus,  often  appear- 
ing as  a  diplococcus. 

Case  V.  March  25th. — Woman,  aged  twenty-four. 
Case  from  Presbyterian  Hospital.  History  of  sore  throat 
and  pseudo-membrane  for  a  week.  Clinical  history  : 
Pharyrx  and  tonsils  swollen  and  livid  red  in  color. 
Considerable  pain  on  swallowing.  Thin,  flaky,  whitish 
pseudo-membrane  on  the  sides  of  the  uvula,  extending 
up  a  short  distance  on  the  soft  palate,  where  the  swelling 
has  caused  creases  of  the  tissues,  also  similar-looking 
patches  on  the  tonsils  and  pharynx.  Temperature  range, 
100  to  101.5°  F. 

Bacterial  examination  :  Many  colonies  of  the  long- 
chained  streptococcus. 

Case  VI.     February    6th. — Margaret    M ,    aged 

twenty  months.  Clinical  history :  Uvula  and  lateral 
walls  of  pharynx  covered  by  thin,  adherent  patches. 

February  8th. — Still  remain  on  uvula.  Temperature 
varies  between  99  and  101°  F. 

February  nth. — Throat  clean. 


32  DIPHTHERIA   AND    ALLIED 

Bacterial  examination  :  Cultures  reveal  many  colonies 
of  the  long  chained  streptococcus. 

This  case  has  an  extremely  interesting  history.  The 
child  was  exposed  to  scarlet  fever  for  three  hours  just 
before  its  admission  to  the  diphtheria  wards  of  the  hos- 
pital. On  the  eighth  day  the  child  developed  scarlet 
fever.  In  two  other  cases,  with  similar  throats,  the  chil- 
dren showed  slight  desquamation  and  are  therefore  con- 
sidered as  complicating  scarlet  fever.  In  this  case  the 
history  excludes  such  a  supposition. 

Case  VII.     February  3,   1892. — Gussie  G ,  aged 

nineteen.  Clinical  history  :  Hyperaemia  of  whole  pharynx 
and  tongue.  Adherent  thin  grayish-white  membrane  on 
sides  and  tip  of  uvula.  A  few  small  grayish  deposits  on 
left  tonsil.  Temperature,  101°  F.  ;  pulse,  98.  On  fifth 
day,  no  membrane ;  feels  well ;  sixth  day,  discharged. 
Temperature,  only  on  two  days  above  100°  F.  On  the 
fourth  day,  trace  of  albumin  in  urine. 

Bacterial  examination  :  Cultures  contained  no  colonies 
of  the  Loeffler  bacilli,  but  many  colonies  of  the  long- 
chained  streptococcus. 

Case  VIII.  February  3d. — Jennie  K ,  aged  eigh- 
teen. Clinical  history :  Thin  adherent  pseudo-membrane 
on  sides  and  tip  of  uvula.  Some  hyperaemia  of  pharynx. 
Temperature,  101.4°  F.;  pulse,  100.  Membrane  re- 
mained four  days.  After  the  first  day,  temperature  and 
pulse  sank  to  the  normal,  and  patient  did  not  appear 
sick.  No  albumin  in  urine.  Discharged  on  the  sixth 
day. 

Bacterial  examination  :  Cultures  revealed  many  colo- 
nies of  the  long-chained  streptococcus  and  numerous 
others  of  various  forms. 

Case   IX.    February    2,     1892. — Mary    D ,    aged 

twenty-one.  Clinical  history  :  For  the  past  three  days, 
pain  on  swallowing  and  on  opening  mouth.  Posterior 
half  of  left  tonsil,  and  post  pillar,  and  most  of  uvula, 
covered  by  a  thin  grayish-white  membrane,  easily  re- 
moved, leaving  only  a  few  bleeding  points.  No  appre- 
ciable ulceration.  Temperature,  102''  F. ;  pulse,  108  j 
respiration,  26.     Glands  of  neck  on  left  side  swollen. 

February  25  th. — Still  thin  white  membrane  on  both 
tonsils  and  adjacent  surfaces  of  uvula. 

Bacterial  examination  :  Plates  and  tubes  gave  a  pure 
culture  of  the  streptococcus. 

Five  other  cases  gave  histories  and  lesions  so  similar  to 
the  above  that  it  seems  needless  to  give  them  in  full. 

Summary. — These  fourteen  cases  present  such  uniform 
clinical  appearances  and  histories  that  they  deserve  to 
be  considered  by  themselves.  The  ages  ranged  from 
twenty  months  to  twenty-one  years.     In  no  case  was  any 


FSEUDO-MEMBRANOUS   INFLAMMATIONS.        33 

clear  history  of  infection  obtained,  or  of  exposure  to 
scarlet  fever  or  measles.  The  considerable  duration, 
three  to  eleven  days,  averaging  five  days,  is  important. 

In  these  cases  there  is  first  a  redness  and  swelling  of 
the  mucous  membrane  of  the  pharynx,  tonsils,  and  fauces, 
with  later  a  thin  purulent  discharge.  Cultures  at  this 
time  reveal  very  abundant  colonies  of  streptococci.  The 
epithelium  of  the  inflamed  mucous  membrane,  where  the 
irritation  is  intensified  by  the  contact  and  friction  of  ad- 
jacent surfaces,  becomes  necrotic,  and  the  denuded  sur- 
face becomes  covered  by  a  thin  pseudo-membrane, 
composed  mostly  of  streptococci  held  together  by  a  small 
amount  of  fibrin.  The  streptococci  may  also  penetrate 
into  the  denuded  mucous  membrane. 

If  one  looks  at  a  well  marked  case,  having  the  patient 
open  the  mouth  slightly,  and  depresses  the  tongue  just  a 
little,  one  will  notice  the  inflamed  uvula  lying  between 
and  against  the  swollen  tonsils.  On  the  portions  of  the 
uvula  thus  irritated  by  contact,  on  the  faucial  pillars  lying 
against  the  tonsils,  and,  in  extreme  cases,  on  the  lateral 
walls  of  the  pharynx  and  on  the  soft  palate  spreading  up 
from  the  sides  of  the  uvula,  one  finds  this  pseudo  mem- 
brane which  is  always  light  grayish  in  color,  thin,  and 
friable.  On  removal,  a  bleeding  surface  is  disclosed. 
When  astringent  applications  are  not  used,  the  membrane 
usually  disappears  gradually,  and  does  not  scale  off  in 
firm  pieces  of  considerable  size,  as  in  many  cases  of  true 
diphtheria. 

In  none  of  these  cases  was  there  a  fatal  result ;  neither 
great  prostration,  after-emaciation,  nor  paralysis.  Except 
that  these  cases  were  never  complicated  by  suppuration 
of  the  cervical  glands  and  diffuse  cellulitis,  they  other- 
wise appear  to  be  the  same  as  the  pseudo-membranous 
inflammations  complicating  scarlet  fever,  the  greater 
severity  in  the  latter  being  probably  due  to  the  influence 
of  the  scarlet  fever.  The  temperature  curve  varied 
greatly  in  the  different  cases.  In  these  fourteen  cases 
the  bacteriological  diagnosis  was  of  great  value  in  prog- 
nosis, for  pseudo- membranes,  so  extensive  in  true  diph- 
theria, would  have  made  it  grave. 

Pseudo-Membranous  Inflammations  Complicating  Scar- 
latina.— Confined  chiefly  to  tonsils,  soft  palate,  and 
pharynx.  Seventeen  of  these  cases  were  repeatedly  ex- 
amined. Except  for  complications,  these  gave  exactly 
the  same  clinical  appearances  as  those  not  complicating 
infectious  diseases.  Only  six  illustrative  cases  will  be 
given. 

Case  I.    February  29th. — James  F ,  aged  two  and 

one-half.  History  of  scarlatinal  rash.  Died.  Clmical 
history  :  Slight  desquamation  on  hands.    There  is  a  thin, 


34  DIPHTHERIA   AND   ALLIED 

gray,  adherent  membrane  on  tonsils.  Temperature, 
1 00°  F. 

March  3d. — Thin,  clean,  grayish  membrane  on  sides 
and  tip  of  uvula. 

March  7th. — Throat  clean. 

March  15th. — This  child,  with  two  others  in  the  ward, 
to-day  showed  a  re-formation  of  the  membrane  on  tonsils 
and  uvula. 

March  i6th. — Considerable  laryngeal  dyspnoea.  Mem- 
brane persists. 

March  i8th. — Intubated.  Bronchial  rales  over  chest. 
Temperature,  loi  to  103°  F.  ;  pulse,  130  to  150;  res- 
piration, 35  to  60.     Broncho  pneumonia. 

March  21st. — Left  cheek  and  lip  swollen  and  oedema- 
tous. 

March  23d. — Extensive  ulceration  of  mucous  mem- 
brane of  left  cheek.  Child  very  weak.  Temperature  and 
pulse  remain  high. 

March  25th. — Tube  removed.  Membrane  disappear- 
ing.    Less  swelling  in  face.     Seems  somewhat  better. 

March  31st. — Gradually  grew  weaker,  with  continued 
high  temperature,  until  death. 

Case  IL     February  9th. — Frank  McM- ,  aged  two. 

Membranous  rhinitis  with  pharyngitis.  Death.  Chnical 
history :  Slight  membrane  on  lateral  walls  of  pharynx. 
Thick,  whitish,  succulent  membrane  blocking  up  both 
nostrils.     Glands  of  neck  swollen. 

February  12th. — Marked  increase  in  inflammation  of 
glands  and  periglandular  tissues.  Pharynx  clean.  Dis- 
integrating membrane  in  nose. 

February  20th.- — Glands  suppurated.  Had  irregular 
high  temperature,  102  to  105°  F.  Pulse  above  150. 
Died  in  septic  condition. 

Bacterial  examination  :  Markedly  twisted  streptococ- 
cus, almost  in  pure  cultures.  No  Loeffler  bacilli  ever 
present.     Bouillon  clear,  with  flocculent  sediment. 

Case  III.    February  9th. — Edna  K ,  aged  two  and 

one-half.  Death.  Clinical  history  :  Tonsils,  adjacent 
edges  of  faucial  pillars,  and  borders  of  uvula,  covered 
by  a  thin,  pearl-colored  pseudo-membrane,  which,  when 
removed,  reveals  ulcerations.  Rash.  Temperature, 
103°  F.  ;  pulse,  156;  respiration,  34.  Patient  died  on 
the  1 8th  with  high  temperature,  pulse,  and  respiration. 

Bacterial  examination  :  Very  numerous  colonies  of  the 
long-chained  streptococci  and  nearly  as  many  of  the 
staphylococcus  pyogenes  aureus. 

Case  IV.    February  7th. — William  W ,  aged  seven. 

Had  had  scarlet  rash  and  high  temperature.  Recovered. 
Clinical  history  :  On  18th,  thin,  whitish  membrane  ad- 
herent to  tonsils.     Glands  of  neck  swollen. 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.        35 

February  2'jth. — Incision  of  suppurating  glands.  Ton- 
sils clean. 

February  29th. — Better  in  every  way.  Temperature  re- 
mained between  99  to  101°  F. 

Bacterial  examination  :  From  throat  and  from  glands 
a  streptococcus,  in  long  twisted  chains,  was  obtained. 
From  the  thin  purulent  serum  from  the  glands  a  pure 
culture  was  secured. 

Case  V.  February  23d. — Annie  O'H .  Recov- 
ered. Clinical  history:  Scarlet  rash;  no  fever;  slight 
hypergemia  of  throat. 

March  17th. — When  apparently  well,  developed  a  thin, 
dirty-white  membrane  on  tonsils,  which  left  a  raw  surface 
on  removal. 

March  19th. — Considerable  ulceration  of  tonsils,  and 
marked  induration  of  glands  of  neck,  with  tenderness. 

March  25th. — Membrane  disappearing. 

From  swab  of  throat  on  February  23d  nearly  pure  cult- 
ure of  the  streptococcus  longus.  From  bit  of  mem- 
brane, March  19th,  almost  pure  culture  of  colonies  of  a 
streptococcus,  appearing  as  a  diplococcus  and  in  short 
rows  under  the  microscope. 

Case   VI.     February   x8,    1892. — Rose   C ,   aged 

three  and  a  half.  Died.  Clinical  history  :  Child  looks 
very  ill.  Thin,  soft  membrane  on  sides  of  uvula,  an- 
terior pillars,  and  lateral  walls  of  pharynx.  When  re- 
moved, leaves  bleeding,  ulcerated  surface.  Glands  of 
neck  swollen. 

February  21st. — Membrane  nearly  gone,  superficial 
ulceration  on  sides  of  uvula.  Glands  hard,  indurated, 
and  much  swollen.  Died  on  2 2d.  Temperature  varied 
between  103  and  105°  F.;  pulse,  160  to  170  ;  respiration, 
44  to  58. 

Bacterial  examination  :  Almost  pure  culture  of  the 
streptococcus. 

Summary  and  Remarks. — In  1 1  other  cases  of  similar 
soft  membrane  on  faucial  pillars,  edges  of  uvula,  and  ton- 
sils, by  far  the  most  numerous  colonies  were  those  of  the 
long- chained  streptococci.  In  one  case  a  streptococcus, 
similar  to  that  occurring  in  the  late  membrane  in  Case 
v.,  was  present.  From  2  cases  of  follicular  tonsillitis, 
and  from  8  cases,  without  exudation,  in  which  hjper- 
gemia  of  pharynx  and  scarlet  rash  were  present,  abundant 
streptococci  were  invariably  found.  In  none  of  the  cases 
were  the  Loeffler  bacilh  found.  Of  the  10  cases  of  scarlet 
fever,  in  which  the  complicating  croupous  inflammation 
appeared  early,  6  died.  In  the  7  in  which  it  appeared 
late,  all  recovered.  In  the  6  fatal  cases,  2  had  extensive 
gangrenous  cellulitis,  beginning  in  the  neck,  spreading 
over  the  chest,  and  causing  the  sloughing  of  an  extensive 


36  DIPHTHERIA   AND   ALLIED 

portion  of  skin.  A  third  had  diffuse  suppuration  in  and 
about  the  cervical  glands. 

The  presence  of  streptococci  growing  in  long  twisted 
chains  in  the  throats  of  all  the  cases  examined  during  the 
period  of  the  eruption  is  very  noteworthy,  and  strorgly 
indicates  the  necessity  of  carefully  looking  after  the 
cleansing  of  the  throats,  whether  any  visible  membrane 
is  present,  or  not.  The  fatal  result  in  some  seemed  to 
be  due  more  to  the  complicating  cellulitis  and  abscesses 
than  to  the  scarlatina.  The  possibility,  suggested  by 
some  observers,  that  the  streptococci  may  be  the  cause 
of  scarlet  fever,  is  worthy  of  investigation.  It  would 
take  very  strong  evidence,  and  necessitate  finding  some 
constant  differences  between  the  streptococci  occurring 
in  scarlet  fever  and  those  appearing  so  frequently  in 
other  conditions,  or  the  proof  that  they  can  at  one  time 
cause  scarlet  fever  and  at  another  a  local  lesion  in  the 
throat.  It  would  seem  more  probable  that  the  mfec- ' 
tious  diseases,  especially  scarlet  fever  and  measles,  favor 
the  development  and  growth  of  the  streptococci,  known 
to  be  so  frequently  present  in  both  the  healthy  and  in- 
flamed throat. 

In  three  of  the  children  who  were  entirely  convalescent 
the  pseudo-membranous  inflammation  seemed  to  be  the 
result  of  an  infection  from  others  in  the  ward.  The 
pseudo-membrane  hning  the  nasal  cavities  in  Case  II.  is 
interesting,  indicating  that  some  cases  of  membranous 
rhinitis  are  due  to  streptococci. 

Pseudo-metJibranes  Involving  Larynx  causea  by  Strepto- 
cocci.— Case  I.     February  13th. — Hattie  S ,  aged  five. 

Recovered.  Clinical  history  :  On  admission,  cyanotic 
from  laryngeal  obstruction;  intubated,  relieved;  very 
slight,  adherent,  thin,  pearl-gray  patches  on  uvula.  Tem- 
perature, 100°  F. ;  pulse,  102;  respiration,  22. 

February  17th. — Patient  never  seemed  sick;  exudation 
on  uvula  disappeared ;  no  albumin  in  urme ;  tube  re- 
mained in  five  days. 

Bacterial  examination  :  Plates  and  tubes,  made  on  two 
days,  showed  no  Loeffler  bacilli,  but  many  colonies  of  a 
long  chained  streptococcus  and  scattering  forms. 

Case  II.     February  14th. — Nochem  E ,  aged  six. 

Recovered.  Clinical  history :  Admitted  with  marked 
laryngeal  stenosis ;  intubation  gave  perfect  relief ;  no 
membrane  visible.  Temperature,  101°  F.;  pulse,  132; 
respiration,  34.  From  time  to  time  some  difficulty  in 
breathing,  which  was  relieved  by  calomel  fumigation. 
For  one  week  temperature  varied  between  99  and  101° 
F. ;  pulse,  100  to  126.  Never  any  visible  membrane. 
No  albumin.     Tube  removed  on  the  fifth  day. 

Bacterial  examination  :  No  Loeffler  colonies  found  on 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.        37 

plates  or  tubes  made  from  swabs  of  pharynx  and  tonsils 
taken  on  the  first  three  days ;  numerous  streptococci. 

Case  III.    March  i6th. — Osthof ,  aged  three  and 

one  half.  Recovered.  Clinical  history  :  Admitted  with 
marked  laryngeal  dyspnoea ;  vomited,  was  fumigated,  but 
without  relief ;  intubated  ;  both  tonsils  covered  by  a 
nearly  white,  thin,  adherent  membrane.  Temperature, 
ioi°  F. ;  pulse,  128  ;  respiration,  30. 

March  19th. — Still  extensive  patches  of  same  mem- 
brane on  tonsils ;  breathes  fairly  well ;  no  prostration. 
On  second  day  temperature  reached  103°  F.     Now  99°  F. 

Bacterial  examination  :  Numerous  colonies  of  strepto- 
cocci ;  none  of  Loeffler  bacilli. 

Case  IV.     March    i8th. — Esther    F ,   aged   one. 

Recovered.  Clmical  history  :  Very  small  white  patch, 
slightly  adherent  to  right  tonsil  ;  laryngeal  dyspnoea ; 
made  to  vomit,  and  fumigated  with  calomel,  but  without 
relief ;  intubated  five  hours  after  arrival.  Temperature, 
99.6°  F. ;  pulse,  120;  respiration,  30. 

March  20th. — Seems  about  well ;  tube  still  retained  ; 
some  albumin  in  urine. 

March  26th. — Tube  removed  ;  temperature  never 
above  100°  F. 

Bacterial  examination  :  Cultures  gave  abundant  col- 
onies of  the  long  chained  streptococcus. 

Case   V.     March    i9ih. — Morris    G ,    aged  four. 

Died.  Clinical  history :  Intubated  before  admission. 
Temperature,  100°  F.  j  pulse,  130;  respiration,  32. 
No  membrane  visible  in  throat  ;  some  white,  flaky  mem- 
brane conghed  up  ;  large  amount  of  albumin  in  the  urine. 

March  22. — Chest  full  of  rales;  child  drowsy  and  cya- 
notic, although  there  is  no  laryngeal  obstruction.  Tem- 
perature, 102°  F. ;  pulse,  150;  respiration,  42.  Swal- 
lows with  difficulty.     Died  on  23d. 

Bacterial  examination  :  Abundant  colonies  of  long- 
chamed  streptococcus  and  many  of  micrococci  and  other 
scattering  forms. 

Case  VI.  March  21st. — Margaret  F--^ — ,  aged  four. 
Clinical  history:  Marked  laryngeal  dyspnoea  on  arrival, 
intubated  one-half  hour  later  ;  large  piece  of  thin,  crum- 
bling membrane  coughed  up  through  tube  ;  swollen  ton- 
sil^, with  small  whitish  patches.  Temperat;ire,  99  4°  F.; 
pulse,  104  ;  respiration,  26. 

March  24th. — Tube  removed;  seems  well;  highest 
temperature,  101°  F.     No  albumin  in  urine. 

Bacterial  examination  :  Cultures  from  swabs  and  from 
membrane  coughed  up  had  many  colonies  of  long- chained 
streptococci  and  some  of  streptococci  appearing  in  short 
rows  and  as  diplococci. 

Case     VII.      March     30th. — Katie      F ,    fifteen 


38  DIPHTHERIA   AND   ALLIED 

months,  sister  of  last.  Clinical  history  :  Five  days  before 
admission  slight  cough,  next  night  awoke  suddenly  with 
croupy  cough.  The  laryngeal  symptoms  increased  from 
night  to  night.  Intubated  shortly  after  admission.  Tem- 
perature, 100.2°  F. ;  pulse,  112;  respiration,  28.  Thin 
whitish  deposits  on  tonsils. 

April  I  St. — Had  an  attack  of  marked  laryngeal  dysp- 
noea, requiring  the  removal  of  the  tube.  Attached  to  it 
was  a  long  piece  of  membrane.  Temperature,  103°  F. ; 
pulse,  144;  respiration,  30.     Restless. 

Patient  developed  broncho -pneumonia.  Temperature 
remained  high.  Tube  was  removed  on  the  eighth  day. 
Died  on  April  loth. 

Bacterial  examination  same  as  in  last. 

These  two  cases  occurring  in  the  same  family,  one 
eight  days  after  the  other,  pomt  to  the  possibility  at  least 
of  a  direct  transmission  of  the  contagion. 

Case  VIIE.     March  3d. — Jennie  P ,  aged  eleven 

months.  Intubation.  Death.  Clinical  history :  Slight 
patches  on  tonsils,  laryngeal  dyspnoea.  "Whole  lower  face 
badly  burned,  through  attempt  of  mother  to  give  it  steam 
inhalations.  Child  looks  badly.  Moist  rales  over  whole 
chest.     Glands  of  neck  slightly  swollen. 

March  4th. — Intubated.  The  tube  keeps  clogging 
with  thick  purulent  fluid.  Dyspnoea  increased,  and  child 
died  at  midnight. 

Bacterial  examination  :  From  first  day  many  strepto- 
cocci, and  many  colonies  of  a  quick-growing  micrococcus, 
which  liquefied  gelatine  and  coagulated  milk.  The 
growth  on  the  media  was  entirely  different  from  the 
staphylococci.  From  trachea,  after  death,  an  almost 
pure  culture  of  the  micrococci  was  obtained. 

Case  IX.     March  17th. — James  F ,  aged  two  and 

one-half.  Intubation.  Death,  Clinical  history  :  On  ac- 
count of  a  previous  history  of  scarlet  fever,  this  case  has 
been  described  under  the  scarlatinal  class. 

Case  X.     March  19th.— William  M ,  aged  thirty. 

From  Presbyterian  Hospital.  Clinical  history  :  No  spe- 
cific, alcoholic,  or  nephritic  history.  Symptoms  began  on 
the  morning  of  the  day  admitted.  When  admitted,  pa- 
tient was  suffering  from  laryngeal  dyspnoea.  Examination 
revealed  much  swelling  and  redness  of  whole  larynx,  also 
a  small  patch  of  moist  membrane  on  arytenoids. 

March  21st. — Dyspncea  was  so  bad  on  the  20th  as  to 
nearly  call  for  tracheotomy.  To-day  breathing  eas  er. 
Soft,  dirty-gray  membrane  persists  on  swollen  arytenoids. 
Small  patches,  also,  on  the  false  cords  and  epiglottis. 
Membrane  disappeared  after  two  days,  and  patient  re- 
covered. The  orderly  who  attended  the  patient  devel- 
oped a  marked  follicular  tonsillitis.     In  both  these  cases 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.        39 


the  most  numerous  colonies  were  those  of  the  strepto- 
coccus growing  in  long  twisted  chains. 

Case  XL  April  27th. — Andrew  I ,  aged  forty- 
three.  Death.  On  admission  the  history  is  obtained 
from  friends  that  he  has  been  three  days  sick.  He  is 
weak,  sightly  delirious,  and  appears  as  if  suffering  from 
some  severe  infectious  disease.  The  whole  uvula  and 
the  portions  of  soft  palate  adjacent  to  it  are  covered  by  a 
very  thin,  dirty  covering  which  can  hardly  be  called  a 
pseudo-membrane.  ■  The  whole  pharynx  and  palate  are 
extremely  hypergemic.  Patient  is  hoarse,  and  has  some 
laryngeal  dyspnoea.  Temperature,  103°  F. ;  pulse,  128; 
respiration,  26.  Patient  became  violently  delirious,  and 
died  the  next  day.     No  autopsy. 

This  case  is  mteresting  as  it  is  the  only  fatal  one  in 
adults.  It  IS  probable  that  the  croupous  inflammation  was 
only  a  complication  of  some  one  of  the  infectious  diseases. 

Pseudo  7?ievibranous  Laryngitis,   not  True    Diphtheria. — 
Table  of  Cases. 


ure, 
and 
.tion 
;al. 

3 

Name. 

Age. 

Disease  and           g    ..h'C 
complications.          g__^  g-  b 

Length  of  time 
intubated. 

Result. 

i        p   3   I)   c 

1      g  0.-  0 

1     H 

I 

Hattie  S. 

5 

Croupous  laryn-  Temp.,  100  ; 

Membrane    re- 

Recovered. 

years.]     gitis;  croupous  '  pulse,  102  ; 

m  a  i  n  e  d    4 

patch  on  uvu-  :  resp.,  22. 

days  ;    i  ntu- 

la.                        1 

baied    for    5 
days. 

a 

Nochem  E 

6 

Croupous  laryn-  Temp.,  loi  ; 

Tube   removed 

Recovered. 

years. 

gitis.                      pulse,  132 ; 
1  r^p.,  34. 

5th  day. 

3 

Harry  0. 

33^ 

Croupous  laryn-  iTemp.,  loi ; 

Tube  removed 

Recovered. 

years. 

gitis;  croupous  1   pulse,  128  ; 
tonsillitis.              resp.,  30. 

Sth  day. 

4 

Esther  F. 

I 

Croupous  laryn-  iTemp.,   99; 

Tube  removed 

Recovered. 

year. 

gitis:  croupous  !  pulse,  120; 
tonsillitis.           i  resp.,  30. 

Sth  day. 

5 

RosieB.. 

sX 

Croupous  laryn- 

Temp.,  99  ; 

Tube  removed 

Recovered. 

years. 

gitis. 

pulse,  1 16  ; 
resp.,  24. 

3d  day. 

6 

Morris  G. 

4 

Croupous  laryn- 

Temp., 102  ; 

Intubated     be- 

Died. 

years. 

gitis  ;  broncho- 
pneumonia. 

pulse,  150 ; 
resp.,  42. 

fore  admis- 
sion ;  lived  4 
days. 
Intubated  with 

7 

Jennie  P . 

II 

Croupous  laryn- 

Temp., 103  ; 

Died. 

mos. 

gitis;  croupous     pulse,  150; 

but  slight  re- 

1 0  n  s  ill  i  tis  ; 

resp.,  40. 

hef ;    lived  i 

scald  of  face ; 

day. 

bronchitis. 

8 

James  F. 

years. 

Extensive  pseu- 
do- membrane 
in  throat;  cellu- 
litis ;  croupous 
la  ry  n  gi  tis  ; 
broncho-pneu- 
monia. 

Temp.,  100. 

19    days    after 
admission  in- 
tubated ;  re- 
moved   after 
7  days. 

Died. 

9 

Barney  S. 

2>!r 

Croupous  larjm-   T  e  m  p  e  ra- 

Intubated  ;   re- 

"Recovered. 

years. 

gltis  ;      devel-  ,   ture,  101.4; 

mo  ve  d  8lh 

■ 

oped    measles     pulse,  106  ; 

day. 

8th  day. 

resp.,  38. 

40 


DIPHTHERIA   AND   ALLIED 


Pseudo-membranous  Laryngitis,  not   True   Diphtheria. — 
Table  of  Cases. — Continued. 


-r-o  a    .' 

S3 

-6 

Name. 

Age. 

Disease  and 
complications. 

Temperaturf 
pulse,   an 
respiratio 
on  arrival. 

Length  of  time 
intubated. 

Result. 

^ 

lO 

Wm.C... 

2 

Croupous  laryn- 

Temp era- 

Intubated  ;  re- 

Recovered. 

years. 

gitis;  croupous 
rhinitis. 

ture,  101.4; 
pulse,  128  ; 
resp.,  38. 

moved  8th 
day. 

11 

Bert.  P  . . 

4 
years. 

Croupous  laryn- 
gitis. 

Temp.,  104  ; 
pulse,  144 ; 
resp.,  48. 

Intubated. 

Recovered. 

12 

KateF... 

15 

Croupous  laryn-  IT  e  m  p  e  ra- 

I  n  t  u  b  a  ted ; 

Died. 

mos. 

gitis;  croupous  |  ture,  100.2; 

lived  II  days. 

t  0  n  s  i  1 1  itis  ; 

pulse,  112  ; 

broncho  pneu- 

resp., 28. 

monia. 

13 

Margt.  F. 

4 

Croupous  laryn- 

Temp. 99.4; 

Intubated  half 

Recovered. 

years. 

gitis;  croupous 
tonsillitis. 

pulse,  T04 ; 
resp.,  26. 

an  hour  after 
a  d  m  i  ssion  ; 
removed    af- 
ter 3  days. 

14 

Harris  A. 

3 

Croupous  laryn- 

Temp. loi  ; 

I  n  tubated    on 

Transferred 

years. 

gitis. 

pulse,  144  ; 
resp.,  40. 

a  d  m  i  ssion  ; 
removed  6th 
day. 

f  0  r   mea- 
sles   9th 
day.  \  «    i| 

IS 

Wm.F.. 

30 

Croupous  laryn- 

Moderately 

Marked   dysp- 

Recovered. 

years. 

gitis. 

high     tem- 
perature. 

noea. 

16 

Andrew  J. 

43 

Croupous  laryn- 

Temp., 103  ; 

Patient  died  in 

Died. 

years. 

gitis  ;  pharyn- 
gitis, etc. 

pulse,  128  ; 
resp.,  26. 

24  hours ;  ap- 
parently had 
s  0  m  e  _  infec- 
tious disease 
besides  crou- 
pous  inflam- 
mation. 

Fourteen  of  these  16  vi^ere  in  young  children.  In  5  of  the  16  no  deposit  or 
membrane  was  visible  above  the  larynx.  Four  of  the  5  deaths  were  due  to  lung 
compUcations. 

Summary. — These  sixteen  cases,  occurring  in  four 
months,  prove  that  membranous  croup  is  frequently  an 
independent  disease,  having  no  connection  with  true 
diphtheria.  In  only  two  was  any  connection  with  scarlet 
fever  or  measles  discovered.  On  admission,  a  diagno- 
sis from  clinical  history  and  appearance  was  impossible. 

In  the  majority  of  the  ten  cases  that  recovered,  the 
course  of  the  disease  was  mild  After  intubation  had  re- 
lieved the  dyspnoea,  the  patients  never  appeared  danger- 
ously ill.  By  the  third  day  they  were  sitting  up  in  their 
beds  and  plajing  with  their  toys.  The  temperature  aver- 
aged somewhat  higher  during  the  first  days  than  in  the 
cases  of  laryngeal  diphtheria,  and  rose  to  103  and  104°  F. 
when  the  lungs  became  involved. 

In  two  of  the  children  a  pretty  clear  history  of  direct 
infection  from  other  cases  was  obtained.  In  croup,  the 
magical  effect  of  intubation  is  seen,  for  without  trache- 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.        4 1 

otomy  or  intubation  the  majority  would  certainly  have 
died.  The  good  percentage  of  recovery,  71 J  per  cent., 
in  these  cases,  as  contrasted  with  intubation  m  diphthe- 
ritic laryngitis,  28^  per  cent.,  throws  much  light  on  the 
problem  why  at  certain  times  and  in  certain  countries 
the  percentage  of  recoveries  is  so  much  greater  than  in 
others.  It  also  forces  the  query  whether,  m  the  future, 
all  cases  should  not  be  examined  bacteriologically,  if  the 
statistics  are  to  be  valuable.  Broncho  pneumonia  seems 
to  be  the  most  frequent  cause  of  death. 

Pseudo  -  membranes  Confined  to  the  Tonsils  Caused  by 

Streptococci. — Case  I.     March  3,  1892. — Genet  M^ , 

aged  six.  CUnical  history  :  From  an  asjlum  with  three 
other  cases.  Right  tonsil  is  swollen  and  covered  by  a 
thick,  adherent,  gray-colored,  fibrinous  pseudo-membrane. 
Cervical  glands  considerably  swollen  on  right  side. 
Slight  pain  and  tenderness.     Temperature,  101°  F. 

March  5th — Still  thick  membrane  on  tonsil.  Nowhere 
else.     Feels  well. 

March  7th. — Tonsil  clean.     Is  slightly  croupy. 

March  9th. — Perfectly  well. 

Bacterial  examination  :  Cover-glass  made  from  smear 
of  membrane  showed  very  numerous  cocci  in  pairs,  sin- 
gly, and  in  chains.  Also  a  few  bacilli.  Plates  gave  an 
almost  pure  culture  of  the  long-chained  streptococcus. 
Nothing  found  in  anyway  similar  to  the  Klebs-Loe filer 
bacillus. 

Case  II. — Mark  C ,  aged  four.  From  same  asy- 
lum. Clinical  history  :  Pseudo-membrane  on  upper  por- 
tion of  left  tonsil  and  adjacent  surface  of  anterior  and 
posterior  pillars.     Well  on  third  day.     No  fever. 

Bacterial  examination  :  Mostly  streptococci. 

Case   III.       March    5,    1892. — Lottie  E ,    aged 

twenty-one.  Clinical  history :  Both  tonsils  are  nearly 
covered  by  irregular,  semi-adherent  pseudo-membranous 
patches.  Considerable  swelling  and  hyperaemia.  No 
swelling  of  glands.  Not  much  pain  ;  slight  constitutional 
symptoms.     Temperature,  101°  F. 

March  7th. — Tonsils  nearly  clean.     Feels  well. 

March  8th. — Perfectly  well. 

Bacterial  examination:  Many  colonies  of  the  long- 
chained  streptococcus  and  other  scattering  forncis. 

Case  IV.     March  12th. — Charles  F ,  aged  thirty. 

Clinical  history  :  Two  days  ago  felt  pain  and  soreness  in 
region  of  tonsils.  Went  to  Bellevue,  and  was  sent  to 
Charity  Hospital.  From  there  taken  to  the  Willard 
Parker  Hospital.  Both  tonsils  covered  by  a  dirty- 
brownish  smear  which  is  readily  removed,  leaving  ir- 
regular patches  on  tonsils.  Pharynx  covered  by  thick, 
purulent  discharge.     Tonsils  and  peritonsillar  tissues  are 


42  DIPHTHERIA   AND    ALLIED 

much  swollen,  and  the  whole  pharynx  and  fauces  hyper- 
£emic.  Considerable  swelling  of  glands  of  neck.  Tem- 
perature, 102°  F.  Great  pain  on  swallowing  and  on  open- 
ing mouth. 

iMarch  14th. — Still  considerable  swelling  and  hyperae- 
mia,  but  membranous  deposits  have  nearly  disappeared. 
Feels  much  better. 

Bacterial  examination  :  Reveals  mostly  colonies  of  the 
long-chained  streptococcus. 

Case    V.     March    13th. — Mary    C -,    aged    four. 

Clinical  history  :  This  child  is  from  the  same  asylum  in 
which  four  cases  occurred  ten  days  before.  Both  tonsils 
are  swollen,  and  covered  by  thick  masses  of  exudate. 
Temperature,  101.4°  F. 

March  i6th. — Tonsils  are  clean.     Patient  feels  well. 

Bacterial  examination  :  Plates  give  nearly  pure  cultures 
of  the  long-chained  streptococcus. 

Case  VI.  March  14th. — Annie  E ,  as:ed  six.  Clin- 
ical history  :  Both  tonsils  covered  by  irregular  patches  of 
pseudo  membrane,  with  intervening  portions  smeared 
with  purulent  discharge.  Considerable  swelling  of  ton- 
sils.    Almost  no  constitutional  disturbance. 

March  i6th. — Tonsils  almost  clean. 

Bacterial  examination  :  The  great  majority  of  the  col- 
onies are  of  streptococci. 

Case  VII.  March  7th. — George  M ,  aged  thirty- 
one.  Clinical  history  :  Felt  chilly  and  depressed  two 
days  ago.  The  next  day  his  physician  on  examination 
found  the  tonsils  swollen  and  covered  with  a  semi-adher- 
ent soft  deposit.  He  was  referred  to  the  Board  of 
Health.  The  first  examiner  thought  it  a  doubtful  case, 
referred  it  to  a  second,  who  pronounced  it  true  diphthe- 
ria. On  admission,  condition  the  same.  Glands  of  neck 
somewhat  swollen. 

March  8th. — Throat  is  clear,  and  he  feels  well. 

Bacterial  examination  :  Majority  of  colonies,  strepto- 
cocci in  long  twisted  chains. 

Case  VIII.  March  nth. — Lahd  F ,  aged  twenty- 
two.  Clinical  history  :  History  of  recurrent  attacks  of 
sore  throat  similar  to  present  one.  Swollen,  irregularly 
excavated  tonsils,  with  a  few  irregular,  gray  deposits. 
Pain  on  swallowing  and  opening  mouth. 

March  14th. — Right  tonsil  nearly  covered  by  dirty  ad- 
herent pseudo  membrane.  Left,  follicular  deposits. 
Less  pain  and  tenderness, 

March  i6th. — Still  small  deposits  on  tonsils. 

March  iSth. — Tonsils  clean. 

Bacterial  examination  :  The  most  numerous  colonies 
are  of  a  rather  quick  growing  streptococcus  which  occurs 
as  a  diplococcus  and  in  short  chains  of  diplococci. 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.        43 

Simwiary. — This  disease  is  so  familiar  that  it  is  unnec- 
essary to  give  more  illustrative  cases.  In  the  159  here 
studied  58  are  included  under  this  heading.  This  com- 
paratively large  number  would  seem  to  indicate  that  in 
adults,  thick  croupous  patches,  adherent  or  not  adherent, 
if  confined  to  the  tonsils,  after  twenty-four  hours  very 
rarely  h'kve  anything  to  do  with  true  diphtheria.  The 
same  bacteria  (the  streptococci)  which  under  certain  in- 
fluences cause  an  inflamed  throat  or  a  follicular  tonsillitis, 
under  others  seem  to  produce  a  croupous  tonsillitis.  In 
several  cases  two  members  of  a  family  were  affected,  one 
with  the  former,  the  other  with  the  latter  disease.  In  a 
few  others  a  very  complete  history  of  direct  transmission 
of  the  contagion  was  obtained.  The  croupous  deposit, 
or  pseudo  membrane,  lasted  from  two  to  seyen  days. 
All  cases  recovered  without  complications. 

The  intimate  connection  of  some  cases  of  croupous 
tonsillitis  with  scarlet  fever  is  brought  out  in  the  follow- 
ing examples  : 

Rose   F ,    aged    twenty- one,    was   admitted,    with 

marked  croupous  tonsillitis  with  constitutional  and  local 
symptoms,  on  May  20th.  The  three  previous  days  she 
had  taken  care  of  a  child  sick  with  scarlet  fever,  and  on 
the  last  day  also  of  the  mother,  who  was  attacked  with 
croupous  tonsillitis.  Both  she  and  the  mother  had  come 
in  frequent  direct  contact  with  the  child. 

Two  physicians  attended  a  gentleman  sick  with  malig- 
nant scarlet  fever  and  croupous  tonsillitis.  Both  were 
attacked  with  croupous  tonsillitis,  and  one  with  scarlet 
fever  also. 

The  streptococci,  found  in  the  pseudo-membranes,  pre- 
sented some  striking  differences.  By  far  the  most  fre- 
quently present  was  a  streptococcus  showing  similar 
morphological  and  biological  traits  to  the  streptococcus 
pyogenes  and  erysipelatus.  This  streptococcus  was  pres- 
ent in  all  the  scarlatinal  cases  during  the  eruption. 
From  the  different  cases  the  cultures  presented  some 
minor  differences  in  the  size  of  the  colonies  and  the  ap- 
pearance of  the  flocculi  in  the  broth.  The  pathogenic 
qualities  varied  greatly.  Inoculations  in  rabbits  from 
some  produced  abscess  and  necrosis,  from  others  merely 
slight  redness  and  swelling. 

During  the  last  two  months,  cultures  from  a  number  of 
cases  presented  a  coccus  which  formed  larger  colonies 
than  the  long-chained  streptococcus  on  the  agar  plates, 
producing  colonies  with  nearly  even  edges,  of  a  coarse, 
granular,  and  blotched  appearance.  Here  and  there, 
from  their  edges  short  runners  sprouted  out,  and  in  some 
cases  short  twisting  loops. 

In  bouillon,  at  37°  C,  the  growth  of  this  streptococcus 


44  DIPHTHERIA   AND   ALLIED 

is  vigorous,  forming,  in  twenty- four  hours,  considerable 
gray  sediment,  with  cloudy  bouillon.  Microscopical  ex- 
amination reveals  diplococci  in  pairs  and  short  rows  of 
four  to  eight.  In  gelatine  tubes  the  growth  does  not 
differ  from  that  of  the  streptococcus  pyogenes  except  in 
that  it  is  somewhat  more  vigorous.  The  few  animal  ex- 
periments made  indicated  it  to  be  less  pathogenic  than 
the  long  chained  streptococcus  in  rabbits.  Injected  in 
the  ears  of  rabbits  it  produced  redness  and  swelling,  from 
the  second  to  the  fifth  day,  with  very  slight  or  moderate 
fever.  The  rabbits  after  the  fifth  day  seemed  well.  In- 
travenous inoculation  was  without  effect  in  two  cases. 
A  third  variety  differed  only  from  the  first,  in  that  the 
loops  were  less  twisted.  One  of  these  forms,  usually  the 
first,  was  the  most  abundant  micro-organism  present  in 
everv  one  of  the  cases  examined,  in  which  the  Klebs- 
Loeffler  bacilli  were  absent.  And  in  cases  of  true  diph- 
theria they  were  usually  present  in  greater  or  lesser  num- 
bers. 

The  staphylococcus  pyogenes  aureus  was  only  irregu- 
larly present  in  the  cases  examined,  and  only  abundant 
in  five.  In  these,  from  the  blood-serum  tubes  alone  one 
would  have  judged  that  they  were  the  most  abundant 
form  of  bacteria,  but  an  early  inspection  of  the  plates 
under  the  microscope  revealed  the  tiny  colonies  of  the 
streptococci  to  be  present  in  far  the  greater  number. 

In  those  cases  in  which  suppuration  of  the  cervical 
glands  and  extensive  cellulitis  was  present,  the  long- 
chained  streptococci  were  always  found,  except  for  such 
complications  the  special  form  of  streptococci  present 
seemed  to  exert  no  influence  on  the  severity  or  length  of 
the  disease. 

G-eneral  Summary. — Bacteria. — In  159  cases  of  pseudo- 
membranous inflammations  there  were  54  in  which  the 
Klebs-Loeffler  or  diphtheria  bacilli  were  present,  usually 
as  the  only  or  most  numerous  form  of  bacteria.  With 
them  were  often  associated  streptococci  and  other  micro- 
organisms. In  every  one  of  the  remaining,  streptococci 
were  the  most  abundant  bacteria,  and  often  the  only 
ones.  From  various  pseudo  membranes  the  streptococci 
obtained  differed  in  manner  of  growth  and  pathogenic 
action.  The  staphylococci  were  often  entirely  absent,  at 
other  times  present  in  moderate  numbers,  but  never  in 
excess  of  the  streptococci. 

Location  of  Lesion. — In  both  diphtheria  and  pseudo- 
diphtheria  the  pseudo-membranes  occurred  on  the  mu- 
cous membrane  of  the  nose,  pharynx,  larynx,  soft  palate, 
and  tonsils.  In  both,  the  tonsils  were  the  parts  most 
frequently  involved.  The  nasal  cavities  were  more  often 
involved  in  true  diphtheria. 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.        45 

Mortality. — In  true  diphtheria,  46^  per  cent.;  in  pseudo- 
diphtheria,  5f  per  cent.;  intubation  in  diphtheria,  71^  per 
cent.;  intubation  in  pseudo-diphtheria,  28^  per  cent.; 
adults  in  diphtheria,  36  per  cent.;  adults  in  pseudo- 
diphtheria,  2  per  cent. 

Contagiousness. — In  quite  a  large  proportion  of  cases 
evidence  was  obtained  of  the  direct  spreading  of  diph- 
theria through  contact  with  infected  persons  and  cloth- 
ing. In  only  a  few  cases  of  pseudo-diphtheria  was 
equally  strong  proof  obtained.  Children  sent  away  from 
diphtheria  for  safety,  carrying  with  them  their  infected 
clothing,  were  in  a  number  of  cases  a  source  of  danger 
to  the  families  who  received  them. 

Clinical  Observations. — It  is  important  at  the  outset 
to  remember  that  true  diphtheria  is  frequently  associated 
with  pseudo  diphtheria,  and  this  mingling  of  the  two  adds 
greatly  to  the  clinical  difficulties.  Severe  uncomplicated 
pseudo  membranous  laryngitis  may  be  either  true  or 
pseudo  diphtheria.  The  early  clinical  diagnosis  is  usu- 
ally impossible.  Low  temperature,  great  prostration, 
and  heart  failure  point  to  true  diphtheria.  A  high  tem- 
perature, lung  complications,  and  no  history  of  infection 
are  in  favor  of  pseudo-diphtheria. 

Death  occurred  usually  early,  due  to  heart  failure  in 
diphtheria ;  usually  later,  due  to  broncho-pneumonia,  in 
pseudo-diphtheria.  In  both,  early  death  from  suffoca- 
tion may  occur,  if  intubation  or  tracheotomy  is  not  per- 
formed. 

Membranous  rhinitis  is  usually  a  very  mild  form  of 
diphtheria  having  a  good  prognosis.  Membranes  com- 
plicating scarlet  fever  are  seldom  true  diphtheria. 
Pseudo  membranes  and  thick  deposits  well  developed 
on,  but  confined  to,  the  tonsils  of  adults  are  nearly  al- 
ways pseudo-diphtheria.  Folhcular  deposits  confined  to 
the  tonsils  in  adults  are  probably  always  pseudo-diph- 
theria. Small  or  large,  thick  or  thin,  firmly  or  slightly 
adherent  patches  confined  to  the  tonsils  or  extending  to 
the  larynx  in  young  children  may  be  either  true  or 
pseudo-diphtheria,  and  the  clinical  diagnosis  is  often  im- 
possible during  any  time  of  the  disease.  Extensive  thin, 
grayish  pseudo-membranes,  occurring  only  on  those  sur- 
faces of  the  uvula,  tonsils,  and  faucial  pillars  which  lie  in 
contact  were  always  pseudo-diphtheria.  The  prognosis 
is  good  in  these  cases,  except  v/hen  there  are  early  com- 
plications of  infectious  diseases. 

The  thick  grayish  or  grayish-yellow  pseudo-membranes 
which  cover  a  large  portion  of  the  soft  palate  and  tonsils, 
often  involving  naso-pharynx  and  nostrils,  were  always 
the  lesion  of  true  diphtheria.  These  cases  were  often 
fatal  in  both  children  and  adults. 


46  DIPHTHERIA   AND    ALLIED 

Conclusions. — The  results  of  previous  investigations, 
with  the  addition  of  that  brought  out  in  these  studies, 
seem  to  force  on  us  the  conclusion  that  there  are  two 
great  divisions  of  pseudo-membranous  inflammations, 
one  caused  by  the  Klebs-Loeffler  bacilli  and  the  other  by 
some  form  of  streptococci.  The  few  cases  in  which  the 
pneumococcus  of  Fraenkel  or  other  cocci  seem  the  cause 
naturally  fall  in  the  second  division. 

The  first  is,  from  beginning  to  end,  a  local  process,  and 
its  lesions  are  due  to  the  effects  of  the  poison  formed  by 
the  bacilli  in  the  pseudo  membrane.  It  is  dangerous  at 
all  periods  of  life.  The  second  is  also  at  first  a  local 
lesion,  but  may  at  any  time  become  a  general  infection. 
It  is  peculiarly  liable  to  cause  broncho-pneumonia  in 
chfildren.  Both  diseases  are  frequently  associated  to- 
gether. Both  are  directly  contagious,  though  in  different 
degrees. 

These  two  diseases,  caused  by  different  bacteria  and 
differing  in  so  many  points,  should  no  longer  be  called  by 
the  same  name.  The  name  diphtheria  will  probably  be 
agreed  upon  by  all  for  those  cases  in  which  the  Klebs- 
Loefiler  bacilli  are  present,  whether  alone  or  associated 
with  other  bacteria. 

For  the  second  division  some  name  will  have  to  be 
agreed  upon ;  whether  the  streptococcus  will  be  found  to 
be  in  such  a  majority  the  cause  that  the  name  strepto- 
coccus diphtheria  can  be  applied  to  it,  only  further  inves- 
tigation can  determine.  Perhaps  at  present  the  term 
pseudo-diphtheria  will  be  acceptable. 

In  all  cases  where  the  diagnosis  is  in  doubt,  bacterio- 
logical examination  should  be  made,  because  : 

1.  A  correct  diagnosis  should  always  be  sought  for. 

2.  Without  it,  all  attempts  to  learn  from  statistics  the 
worth  of  special  forms  of  treatment  and  methods  of  pre- 
vention are  well-nigh  useless  from  the  frequent  incor- 
rectness of  the  diagnosis.  The  fact  that  during  four 
months  less  than  one-third  of  the  cases  sent  to  the  diph- 
theria wards  of  the  hospital  had  true  diphtheria,  is  sufii- 
cent  proof  of  the  difficulty  of  making  a  clinical  diagnosis. 

3.  It  is  a  great  help  to  prognosis  and  rational  treat- 
ment in  the  more  severe  cases  and  enables  us  to  take 
measures  more  effectually  to  prevent  the  spread  of  the 
contagion. 

4.  It  is  certain,  can  frequently  be  made  immediately, 
and  always  within  twenty  hours. 

The  amount  of  familiarity  with  bacteriological  work 
and  the  appliances  necessary,  although  not  very  great,  are 
still  enough  to  prevent  the  great  majority  of  physicians 
from  undertaking  it  themselves.  As  the  early  detection 
of  diphtheria  is  important  for  the  general  health,  and  as 


PSEUDO-MEMBRANOUS   INFLAMMATIONS.       4/ 

this  disease  occurs  most  frequently  and  is  most  danger- 
ous among  the  crowded  poor,  who  are  unable  to  pay  for 
special  examination,  it  would  seem  peculiarly  the  business 
of  the  Boards  of  Health  to  undertake  it.  In  small  cities 
some  central  place  could  be  selected  where  the  neces- 
sary appliances  could  be  kept,  in  large  cities  several 
would  be  necessary.  From  these  laboratories  a  properly 
equipped  man  could  be  called  to  make  the  cultures  and 
give  the  bacteriological  diagnosis.  Children's  hospitals 
and  those  for  infectious  diseases  should  certainly  give 
their  pathologist  the  means  to  do  this. 

To  insure  the  safety  of  those  not  having  diphtheria, 
these  hospitals  should  have  wards  separated,  where  doubt- 
ful cases  could  be  kept  for  twenty-four  hours  until  the 
diagnosis  was  made  certain  by  bacteriological  examma- 
tions.  Where  this  is  impossible,  experience  at  the  Wil- 
lard  Parker  Hospital  has  shown  that  general  cleanliness 
and  antiseptic  irrigation  of  the  nasal  and  pharyngeal  mu- 
cous membranes  is  sufficient  in  the  great  majority  of  cases 
to  prevent  the  spreading  of  diphtheria.  Care  should  be 
taken  not  to  expose  small  children  to  pseudo-diphtheria, 
for  it  is  undoubtedly  contagious  under  favorable  condi- 
tions and  is  in  them  dangerous. 

I  wish,  in  closing,  to  express  my  gratitude  to  Professor 
T.  Mitchell  Prudden,  Director  of  the  Pathological  La- 
boratories of  the  College  of  Physicians  and  Surgeons  of 
Columbia  College,  New  York,  for  his  kindress  in  making 
many  valuable  suggestions  and  in  affording  me  every 
needed  laboratory  facility  for  these  investigations. 

I  also  wish  to  thank  Dr.  T.  W.  Lester,  Resident  Phy- 
sician to  the  Willard  Parker  Hospital,  for  his  help  in  the 
clinical  part  of  these  studies,  and  for  the  use  of  the  hospi- 
tal charts. 

128  West  Eleventh  Street,  July  i,  1892. 
References. 

1  Loefifler  :  Deutsche  Med.  Wochenschrift,  1890,  Num.  5  und  6. 

2  Welch  :  Medical  News,  May  16,  1891. 

3  Klebs  :  Verhandl.  des  zweiten  Congress  f.  Inn.  Med.,  1883. 

4  Loeffler  :   Mitth.  a.  d.  Kais.  Gesundheitsamte,  Bd.  2,  1884. 

^  Roux  and  Yersin :  Annales  de  I'lnst.  Pasteur,  ii. ,  1888,  p.  629; 
iii.,  i88g,  p.  273  ;  iv.,  1890,  p.   384. 

6  Kolisko  and  Paltauf :  Wiener  klin.  Wochen.,  1889,  No.  8. 

"<  Ortmann :   Berlin   klin.  Woch. ,  1889.  No.  10,  p.  18. 

8  Zarniko  :  Centralbl.  f.  Bact. ,  vi.,  1889,  p.  154. 

8  Escherich  :  Centralbl.  f.  Bact.,  vii. ,  1890. 

1"  Beck  :  Zeitschrift  f.  Hygiene,  viii. ,  1890  ;  Heft  3,  p.  434. 

i','-Brieger  and  Fraenkel :  Berlin,  klm.  Wochen.,  1890,  Num.  11 
und  12. 

"  Tangl :    Centralbl.  f.  Allg.  Path,    und  Path.  Anat.,  1890,  Bd.  i, 

P-  795- 

'■'  Babes  :  Zeitschrift  fiir  Hygiene,  Bd.  5,  p.  177. 

16  D'Espine  :    Revue  medicale  de  la  Suisse  ro.,  1888,  No.  i,  p.  49. 

i«  Klein:  a,  Centralbl.  f.  Bact.,  vii.,  1890,  No.  17;  5,  Centralbl.  f. 
Bact.,  vii.,  1890,  No.  25. 


48  DIPHTHERIA. 

17  Welch  and  Abbott :   Bulletin  of  the   Johns   Hopkins    Hospital, 
February-March,  1891. 

'8  Prudden :  Medical  Record,  April  18.  1891. 

1^  Roux  and  Yersin-:  Annales  de  I'lnstitut  Pasteur,  iii. ,  1889,  p.  273. 

20  Fraenkel  and  Brieger  :   Berlin,  klin.  Woch.,  December  3,  i8go. 

21  Babes  :  Virch.  Archiv.,  Bd.  119,  S.  468. 

22  Welch  and  Flexnor  i  Bulletin  of  the  Johns   Hopkins  Hospital, 
August,  1891,  March,  1892. 

23  Behring  and  Wernicke  :  Zeit.  Hygiene  u.  Infect.  Krank. ,  Bd.  12, 
H.  I,  S.  ID. 

2*  Brieger,  Kitasato,  and  Wasserman :  Zeit.   Hyg.  u.  Inn.  Krank., 
Bd.  xii.,  H.  I,  No.  2.  25  ibid. 

28  Barbier  :    Arch,  de  Medecine  Exp6r.,  1891,  p.  68. 

27  Abbott :    Bulletin  of  the  Johns  Hopkins  Hospital,  October-No- 
vember, 1891. 
2s  Roux  and  Yersin :  Annales  de  I'lnst.  Past.,  1889,  p.  273. 

29  Loeffler  :  Mitth.  a.  d.  Kais.  Gesund.,  Bd.  2,  1884. 

3"  Prudden  :    American  Journal   of  the  Medical   Sciences,   April, 
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31  Prudden   and   Northrup :    American   Journal    of   the    Medical 
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32  Wurz  and  Bourges  :  Archives  de  Medecine  Experiment.,  May  i, 
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33  Sevestre  :  Centralbl.  f.  Bakt.,  August  29,  1890,  p.  301. 

34  Tangl  :  Centralbl.  f  Bakt.,  July  8,  1891. 

35  Baginsky  :  Berlin,  klin.  Wochen. ,  February  29,  1892. 
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